BMC Biophysics最新文献

{"title":"Molecular dynamics simulations indicate an induced-fit mechanism for LSD1/CoREST-H3-histone molecular recognition.","authors":"Nadeem A Vellore,&nbsp;Riccardo Baron","doi":"10.1186/2046-1682-6-15","DOIUrl":"https://doi.org/10.1186/2046-1682-6-15","url":null,"abstract":"<p><strong>Background: </strong>Lysine Specific Demethylase (LSD1 or KDM1A) in complex with its co-repressor protein CoREST catalyzes the demethylation of the H3 histone N-terminal tail and is currently one of the most promising epigenetic targets for drug discovery against cancer and neurodegenerative diseases. Models of non-covalent binding, such as lock and key, induced-fit, and conformational selection could help explaining the molecular mechanism of LSD1/CoREST-H3-histone association, thus guiding drug discovery and design efforts. Here, we quantify the extent to which LSD1/CoREST substrate binding is consistent with these hypothetical models using LSD1/CoREST conformational ensembles obtained through extensive explicit solvent molecular dynamics (MD) simulations.</p><p><strong>Results: </strong>We find that an induced-fit model is the most representative of LSD1/CoREST-H3-histone non-covalent binding and accounts for the local conformational changes occurring in the H3-histone binding site. We also show that conformational selection - despite in principle not ruled out by this finding - is minimal, and only relevant when global properties are considered, e.g. the nanoscale motion of the LSD1/CoREST clamp.</p><p><strong>Conclusion: </strong>The induced-fit mechanism revealed by our MD simulation study will aid the inclusion of protein dynamics for the discovery and design of LSD1 inhibitors targeting the H3-histone binding region. On a general basis, our study indicates the importance of using multiple metrics or selection schemes when testing alternative hypothetical mechanistic models of non-covalent binding.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":"6 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2013-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2046-1682-6-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31900979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exact approach for studying cargo transport by an ensemble of molecular motors.","authors":"Donatello Materassi,&nbsp;Subhrajit Roychowdhury,&nbsp;Thomas Hays,&nbsp;Murti Salapaka","doi":"10.1186/2046-1682-6-14","DOIUrl":"https://doi.org/10.1186/2046-1682-6-14","url":null,"abstract":"<p><strong>Background: </strong>Intracellular transport is crucial for many cellular processes where a large fraction of the cargo is transferred by motor-proteins over a network of microtubules. Malfunctions in the transport mechanism underlie a number of medical maladies.Existing methods for studying how motor-proteins coordinate the transfer of a shared cargo over a microtubule are either analytical or are based on Monte-Carlo simulations. Approaches that yield analytical results, while providing unique insights into transport mechanism, make simplifying assumptions, where a detailed characterization of important transport modalities is difficult to reach. On the other hand, Monte-Carlo based simulations can incorporate detailed characteristics of the transport mechanism; however, the quality of the results depend on the number and quality of simulation runs used in arriving at results. Here, for example, it is difficult to simulate and study rare-events that can trigger abnormalities in transport.</p><p><strong>Results: </strong>In this article, a semi-analytical methodology that determines the probability distribution function of motor-protein behavior in an exact manner is developed. The method utilizes a finite-dimensional projection of the underlying infinite-dimensional Markov model, which retains the Markov property, and enables the detailed and exact determination of motor configurations, from which meaningful inferences on transport characteristics of the original model can be derived.</p><p><strong>Conclusions: </strong>Under this novel probabilistic approach new insights about the mechanisms of action of these proteins are found, suggesting hypothesis about their behavior and driving the design and realization of new experiments.The advantages provided in accuracy and efficiency make it possible to detect rare events in the motor protein dynamics, that could otherwise pass undetected using standard simulation methods. In this respect, the model has allowed to provide a possible explanation for possible mechanisms under which motor proteins could coordinate their motion.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":"6 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2013-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2046-1682-6-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31869990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparative study of ribosomal proteins: linkage between amino acid distribution and ribosomal assembly.","authors":"Brittany Burton Lott, Yongmei Wang, Takuya Nakazato","doi":"10.1186/2046-1682-6-13","DOIUrl":"10.1186/2046-1682-6-13","url":null,"abstract":"<p><strong>Background: </strong>Assembly of the ribosome from its protein and RNA constituents must occur quickly and efficiently in order to synthesize the proteins necessary for all cellular activity. Since the early 1960's, certain characteristics of possible assembly pathways have been elucidated, yet the mechanisms that govern the precise recognition events remain unclear.We utilize a comparative analysis to investigate the amino acid composition of ribosomal proteins (r-proteins) with respect to their role in the assembly process. We compared small subunit (30S) r-protein sequences to those of other housekeeping proteins from 560 bacterial species and searched for correlations between r-protein amino acid content and factors such as assembly binding order, environmental growth temperature, protein size, and contact with ribosomal RNA (rRNA) in the 30S complex.</p><p><strong>Results: </strong>We find r-proteins have a significantly high percent of positive residues, which are highly represented at rRNA contact sites. An inverse correlation between the percent of positive residues and r-protein size was identified and is mainly due to the content of Lysine residues, rather than Arginine. Nearly all r-proteins carry a net positive charge, but no statistical correlation between the net charge and the binding order was detected. Thermophilic (high-temperature) r-proteins contain increased Arginine, Isoleucine, and Tyrosine, and decreased Serine and Threonine compared to mesophilic (lower-temperature), reflecting a known distinction between thermophiles and mesophiles, possibly to account for protein thermostability. However, this difference in amino acid content does not extend to rRNA contact sites, as the proportions of thermophilic and mesophilic contact residues are not significantly different.</p><p><strong>Conclusions: </strong>Given the significantly higher level of positively charged residues in r-proteins and at contact sites, we conclude that ribosome assembly relies heavily on an electrostatic component of interaction. However, the binding order of r-proteins in assembly does not appear to depend on these electrostatics interactions. Additionally, because thermophiles and mesophiles exhibit significantly different amino acid compositions in their sequences but not in the identities of contact sites, we conclude that this electrostatic component of interaction is insensitive to temperature and is not the determining factor differentiating the temperature sensitivity of ribosome assembly.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":" ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2013-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40258214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-consistent field theory for the interactions between keratin intermediate filaments.","authors":"Anna Akinshina,&nbsp;Etienne Jambon-Puillet,&nbsp;Patrick B Warren,&nbsp;Massimo G Noro","doi":"10.1186/2046-1682-6-12","DOIUrl":"https://doi.org/10.1186/2046-1682-6-12","url":null,"abstract":"<p><strong>Background: </strong>Keratins are important structural proteins found in skin, hair and nails. Keratin Intermediate Filaments are major components of corneocytes, nonviable horny cells of the Stratum Corneum, the outermost layer of skin. It is considered that interactions between unstructured domains of Keratin Intermediate Filaments are the key factor in maintaining the elasticity of the skin.</p><p><strong>Results: </strong>We have developed a model for the interactions between keratin intermediate filaments based on self-consistent field theory. The intermediate filaments are represented by charged surfaces, and the disordered terminal domains of the keratins are represented by charged heteropolymers grafted to these surfaces. We estimate the system is close to a charge compensation point where the heteropolymer grafting density is matched to the surface charge density. Using a protein model with amino acid resolution for the terminal domains, we find that the terminal chains can mediate a weak attraction between the keratin surfaces. The origin of the attraction is a combination of bridging and electrostatics. The attraction disappears when the system moves away from the charge compensation point, or when excess small ions and/or NMF-representing free amino acids are added.</p><p><strong>Conclusions: </strong>These results are in concordance with experimental observations, and support the idea that the interaction between keratin filaments, and ultimately in part the elastic properties of the keratin-containing tissue, is controlled by a combination of the physico-chemical properties of the disordered terminal domains and the composition of the medium in the inter-filament region.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":"6 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2013-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2046-1682-6-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31709501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetic effects of TiO2 fine particles and nanoparticles aggregates on the nanomechanical properties of human neutrophils assessed by force spectroscopy.","authors":"Everton Luis Santos da Rosa","doi":"10.1186/2046-1682-6-11","DOIUrl":"https://doi.org/10.1186/2046-1682-6-11","url":null,"abstract":"<p><strong>Background: </strong>Increasing applications of titanium dioxide (TiO2) fine particles (FPs) and nanoparticles (NPs) require coupled knowledge improvement concerning their biokinetic effects. Neutrophils are quickly recruited to titanium implantation areas. Neutrophils mechanical properties display a crucial role on cell physiology and immune responsive functions. Then, micro and nanomechanical characterization assessed by force spectroscopy (FS) technique has been largely applied in this field.</p><p><strong>Results: </strong>Scanning electron microscopy (SEM) images highlighted neutrophils morphological changes along TiO2 FPs and NPs aggregates exposure time (1, 5, and 30 min) compared to controls. FS approaches showed an increasing on attraction forces to TiO2 FPs and NPs treated neutrophils. This group depicted stronger stiffness features than controls just at 1 min of exposure. Treated neutrophils showed a tendency to increase adhesive properties after 1 and 5 min of exposure. These cells maintained comparatively higher elasticity behavior for a longer time possibly due to intense phagocytosis and cell stiffness opposing to the tip indentation. Neutrophils activation caused by FPs and NPs uptake could be related to increasing dissipated energy results.</p><p><strong>Conclusions: </strong>Mechanical modifications resulted from TiO2 FPs and NPs aggregates interaction with neutrophils showed increasing stiffness and also cell morphology alteration. Cells treatment by this metal FPs and NPs caused an increase in attractive forces. This event was mainly observed on the initial exposure times probably regarding to the interaction of neutrophils membrane and phagocytosis. Similar results were found to adhesion forces and dissipated energy outcomes. Treated cells presented comparatively higher elasticity behavior for a longer time. SEM images clearly suggested cell morphology alteration along time course probably related to activation, cytoskeleton rearrangement and phagocytosis. This scenario with increase in stiffness strongly suggests a direct relationship over neutrophil rolling, arrest, and transmigration. Scrutinizing these interactions represents an essential step to clarify the mechanisms involved on treatments containing micro and nanomaterials and their fates on the organisms.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":"6 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2013-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2046-1682-6-11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31667333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular basis of HHQ biosynthesis: molecular dynamics simulations, enzyme kinetic and surface plasmon resonance studies.","authors":"Anke Steinbach,&nbsp;Christine K Maurer,&nbsp;Elisabeth Weidel,&nbsp;Claudia Henn,&nbsp;Christian Brengel,&nbsp;Rolf W Hartmann,&nbsp;Matthias Negri","doi":"10.1186/2046-1682-6-10","DOIUrl":"https://doi.org/10.1186/2046-1682-6-10","url":null,"abstract":"<p><strong>Background: </strong>PQS (PseudomonasQuinolone Signal) and its precursor HHQ are signal molecules of the P. aeruginosa quorum sensing system. They explicate their role in mammalian pathogenicity by binding to the receptor PqsR that induces virulence factor production and biofilm formation. The enzyme PqsD catalyses the biosynthesis of HHQ.</p><p><strong>Results: </strong>Enzyme kinetic analysis and surface plasmon resonance (SPR) biosensor experiments were used to determine mechanism and substrate order of the biosynthesis. Comparative analysis led to the identification of domains involved in functionality of PqsD. A kinetic cycle was set up and molecular dynamics (MD) simulations were used to study the molecular bases of the kinetics of PqsD. Trajectory analysis, pocket volume measurements, binding energy estimations and decompositions ensured insights into the binding mode of the substrates anthraniloyl-CoA and β-ketodecanoic acid.</p><p><strong>Conclusions: </strong>Enzyme kinetics and SPR experiments hint at a ping-pong mechanism for PqsD with ACoA as first substrate. Trajectory analysis of different PqsD complexes evidenced ligand-dependent induced-fit motions affecting the modified ACoA funnel access to the exposure of a secondary channel. A tunnel-network is formed in which Ser317 plays an important role by binding to both substrates. Mutagenesis experiments resulting in the inactive S317F mutant confirmed the importance of this residue. Two binding modes for β-ketodecanoic acid were identified with distinct catalytic mechanism preferences.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":"6 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2046-1682-6-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31633836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions of the amphiphiles arbutin and tryptophan with phosphatidylcholine and phosphatidylethanolamine bilayers in the dry state.","authors":"Antoaneta V Popova,&nbsp;Dirk K Hincha","doi":"10.1186/2046-1682-6-9","DOIUrl":"https://doi.org/10.1186/2046-1682-6-9","url":null,"abstract":"<p><strong>Background: </strong>Water is essential for life, but some organisms can survive complete desiccation, while many more survive partial dehydration during drying or freezing. The function of some protective molecules, such as sugars, has been extensively studied, but much less is known about the effects of amphiphiles such as flavonoids and other aromatic compounds. Amphiphiles may be largely soluble under fully hydrated conditions, but will partition into membranes upon removal of water. Little is known about the effects of amphiphiles on membrane stability and how amphiphile structure and function are related. Here, we have used two of the most intensively studied amphiphiles, tryptophan (Trp) and arbutin (Arb), along with their isolated hydrophilic moieties glycine (Gly) and glucose (Glc) to better understand structure-function relationships in amphiphile-membrane interactions in the dry state.</p><p><strong>Results: </strong>Fourier-transform infrared (FTIR) spectroscopy was used to measure gel-to-liquid crystalline phase transition temperatures (Tm) of liposomes formed from phosphatidylcholine and phosphatidylethanolamine in the presence of the different additives. In anhydrous samples, both Glc and Arb strongly depressed Tm, independent of lipid composition, while Gly had no measurable effect. Trp, on the other hand, either depressed or increased Tm, depending on lipid composition. We found no evidence for strong interactions of any of the compounds with the lipid carbonyl or choline groups, while all additives except Gly seemed to interact with the phosphate groups. In the case of Arb and Glc, this also had a strong effect on the sugar OH vibrations in the FTIR spectra. In addition, vibrations from the hydrophobic indole and phenol moieties of Trp and Arb, respectively, provided evidence for interactions with the lipid bilayers.</p><p><strong>Conclusions: </strong>The two amphiphiles Arb and Trp interact differently with dry bilayers. The interactions of Arb are dominated by contributions of the Glc moiety, while the indole governs the effects of Trp. In addition, only Trp-membrane interactions showed a strong influence of lipid composition. Further investigations, using the large structural diversity of plant amphiphiles will help to understand how their structure determines the interaction with membranes and how that influences their biological functions, for example under freezing or dehydration conditions.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":"6 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2013-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2046-1682-6-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31601588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drop drying on surfaces determines chemical reactivity - the specific case of immobilization of oligonucleotides on microarrays.","authors":"Jens Sobek,&nbsp;Catharine Aquino,&nbsp;Wilfried Weigel,&nbsp;Ralph Schlapbach","doi":"10.1186/2046-1682-6-8","DOIUrl":"https://doi.org/10.1186/2046-1682-6-8","url":null,"abstract":"<p><strong>Background: </strong>Drop drying is a key factor in a wide range of technical applications, including spotted microarrays. The applied nL liquid volume provides specific reaction conditions for the immobilization of probe molecules to a chemically modified surface.</p><p><strong>Results: </strong>We investigated the influence of nL and μL liquid drop volumes on the process of probe immobilization and compare the results obtained to the situation in liquid solution. In our data, we observe a strong relationship between drop drying effects on immobilization and surface chemistry. In this work, we present results on the immobilization of dye labeled 20mer oligonucleotides with and without an activating 5'-aminoheptyl linker onto a 2D epoxysilane and a 3D NHS activated hydrogel surface.</p><p><strong>Conclusions: </strong>Our experiments identified two basic processes determining immobilization. First, the rate of drop drying that depends on the drop volume and the ambient relative humidity. Oligonucleotides in a dried spot react unspecifically with the surface and long reaction times are needed. 3D hydrogel surfaces allow for immobilization in a liquid environment under diffusive conditions. Here, oligonucleotide immobilization is much faster and a specific reaction with the reactive linker group is observed. Second, the effect of increasing probe concentration as a result of drop drying. On a 3D hydrogel, the increasing concentration of probe molecules in nL spotting volumes accelerates immobilization dramatically. In case of μL volumes, immobilization depends on whether the drop is allowed to dry completely. At non-drying conditions, very limited immobilization is observed due to the low oligonucleotide concentration used in microarray spotting solutions. The results of our study provide a general guideline for microarray assay development. They allow for the initial definition and further optimization of reaction conditions for the immobilization of oligonucleotides and other probe molecule classes to different surfaces in dependence of the applied spotting and reaction volume.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":"6 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2013-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2046-1682-6-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31500090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells.","authors":"Marina S Dietz,&nbsp;Daniel Haße,&nbsp;Davide M Ferraris,&nbsp;Antonia Göhler,&nbsp;Hartmut H Niemann,&nbsp;Mike Heilemann","doi":"10.1186/2046-1682-6-6","DOIUrl":"https://doi.org/10.1186/2046-1682-6-6","url":null,"abstract":"<p><strong>Background: </strong>The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane.</p><p><strong>Results: </strong>To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding.</p><p><strong>Conclusions: </strong>Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":"6 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2013-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2046-1682-6-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31570182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of signaling receptors: do ligands bind to receptor monomer, dimer, or both?","authors":"Xiaodong Pang,&nbsp;Huan-Xiang Zhou","doi":"10.1186/2046-1682-6-7","DOIUrl":"https://doi.org/10.1186/2046-1682-6-7","url":null,"abstract":"<p><p>A recent study by Dietz et al. using single-molecule fluorescence microscopy techniques demonstrates that, in the absence of the ligand InlB, the MET receptor exists as both a monomer and a dimer on the cell membrane, and addition of the ligand leads to increased MET dimerization. Under the crowded conditions of the cell membrane, dimer formation may be a common phenomenon for cell surface receptors. Ligand binding to both monomeric and dimeric receptors may provide parallel routes to receptor activation.</p>","PeriodicalId":9045,"journal":{"name":"BMC Biophysics","volume":"6 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2013-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2046-1682-6-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31477644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}