Current Research in Structural Biology最新文献

{"title":"Energy landscape of the SARS-CoV-2 reveals extensive conformational heterogeneity","authors":"Ghoncheh Mashayekhi ,&nbsp;John Vant ,&nbsp;Abhigna Polavarapu ,&nbsp;Abbas Ourmazd ,&nbsp;Abhishek Singharoy","doi":"10.1016/j.crstbi.2022.02.001","DOIUrl":"10.1016/j.crstbi.2022.02.001","url":null,"abstract":"<div><p>Cryo-electron microscopy (cryo-EM) has produced a number of structural models of the SARS-CoV-2 spike, already prompting biomedical outcomes. However, these reported models and their associated electrostatic potential maps represent an unknown admixture of conformations stemming from the underlying energy landscape of the spike protein. As with any protein, some of the spike's conformational motions are expected to be biophysically relevant, but cannot be interpreted only by static models. Using experimental cryo-EM images, we present the energy landscape of the glycosylated spike protein, and identify the diversity of low-energy conformations in the vicinity of its open (so called 1RBD-up) state. The resulting atomic refinement reveal global and local molecular rearrangements that cannot be inferred from an average 1RBD-up cryo-EM model. Here we report varied degrees of “openness” in global conformations of the 1RBD-up state, not revealed in the single-model interpretations of the density maps, together with conformations that overlap with the reported models. We discover how the glycan shield contributes to the stability of these low-energy conformations. Five out of six binding sites we analyzed, including those for engaging ACE2, therapeutic mini-proteins, linoleic acid, two different kinds of antibodies, switch conformations between their known apo- and holo-conformations, even when the global spike conformation is 1RBD-up. This apo-to-holo switching is reminiscent of a conformational preequilibrium. We found only one binding site, namely that of AB-C135 remains in apo state within all the sampled free energy-minimizing models, suggesting an induced fit mechanism for the docking of this antibody to the spike.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 68-77"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4f/91/main.PMC8902891.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10487902","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":"Mechanism of RNA recognition by a Musashi RNA-binding protein","authors":"Jinan Wang ,&nbsp;Lan Lan ,&nbsp;Xiaoqing Wu ,&nbsp;Liang Xu ,&nbsp;Yinglong Miao","doi":"10.1016/j.crstbi.2021.12.002","DOIUrl":"10.1016/j.crstbi.2021.12.002","url":null,"abstract":"<div><p>The Musashi RNA-binding proteins (RBPs) regulate translation of target mRNAs and maintenance of cell stemness and tumorigenesis. Musashi-1 (MSI1), long considered as an intestinal and neural stem cell marker, has been more recently found to be over expressed in many cancers. It has served as an important drug target for treating acute myeloid leukemia and solid tumors such as ovarian, colorectal and bladder cancer. One of the reported binding targets of MSI1 is Numb, a negative regulator of the Notch signaling. However, the dynamic mechanism of Numb RNA binding to MSI1 remains unknown, largely hindering effective drug design targeting this critical interaction. Here, we have performed extensive all-atom microsecond-timescale simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method, which successfully captured multiple times of spontaneous and highly accurate binding of the Numb RNA from bulk solvent to the MSI1 protein target site. GaMD simulations revealed that Numb RNA binding to MSI1 involved largely induced fit in both the RNA and protein. The simulations also identified important low-energy intermediate conformational states during RNA binding, in which Numb interacted mainly with the β2-β3 loop and C terminus of MSI1. The mechanistic understanding of RNA binding obtained from our GaMD simulations is expected to facilitate rational structure-based drug design targeting MSI1 and other RBPs.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 10-20"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ec/3e/main.PMC8695263.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39649771","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":"HPMPdb: A machine learning-ready database of protein molecular phenotypes associated to human missense variants","authors":"Daniele Raimondi ,&nbsp;Francesco Codicè ,&nbsp;Gabriele Orlando ,&nbsp;Joost Schymkowitz ,&nbsp;Frederic Rousseau ,&nbsp;Yves Moreau","doi":"10.1016/j.crstbi.2022.04.004","DOIUrl":"10.1016/j.crstbi.2022.04.004","url":null,"abstract":"<div><p>Current human Single Amino acid Variants (SAVs) databases provide a link between a SAVs and their effect on the carrier individual phenotype, often dividing them into Deleterious/Neutral variants. This is a very coarse-grained description of the genotype-to-phenotype relationship because it relies on un-realistic assumptions such as the perfect Mendelian behavior of each SAV and considers only dichotomic phenotypes. Moreover, the link between the effect of a SAV on a protein (its molecular phenotype) and the individual phenotype is often very complex, because multiple level of biological abstraction connect the protein and individual level phenotypes. Here we present HPMPdb, a manually curated database containing human SAVs associated with the detailed description of the molecular phenotype they cause on the affected proteins. With particular regards to machine learning (ML), this database can be used to let researchers go beyond the existing Deleterious/Neutral prediction paradigm, allowing them to build molecular phenotype predictors instead. Our class labels describe in a succinct way the effects that each SAV has on 15 protein molecular phenotypes, such as protein-protein interaction, small molecules binding, function, post-translational modifications (PTMs), sub-cellular localization, mimetic PTM, folding and protein expression. Moreover, we provide researchers with all necessary means to re-producibly train and test their models on our database. The webserver and the data described in this paper are available at hpmp.esat.kuleuven.be.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 167-174"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X22000125/pdfft?md5=d27cdb5d3a4326b327b8edd15547ebac&pid=1-s2.0-S2665928X22000125-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41376490","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":"Bridging the N-terminal and middle domains in FliG of the flagellar rotor","authors":"Dagnija Tupiņa ,&nbsp;Alexander Krah ,&nbsp;Jan K. Marzinek ,&nbsp;Lorena Zuzic ,&nbsp;Adam A. Moverley ,&nbsp;Chrystala Constantinidou ,&nbsp;Peter J. Bond","doi":"10.1016/j.crstbi.2022.02.002","DOIUrl":"10.1016/j.crstbi.2022.02.002","url":null,"abstract":"<div><p>Flagella are necessary for bacterial movement and contribute to various aspects of virulence. They are complex cylindrical structures built of multiple molecular rings with self-assembly properties. The flagellar rotor is composed of the MS-ring and the C-ring. The FliG protein of the C-ring is central to flagellar assembly and function due to its roles in linking the C-ring with the MS-ring and in torque transmission from stator to rotor. No high-resolution structure of an assembled C-ring has been resolved to date, and the conformation adopted by FliG within the ring is unclear due to variations in available crystallographic data. Here, we use molecular dynamics (MD) simulations to study the conformation and dynamics of FliG in different states of assembly, including both in physiologically relevant and crystallographic lattice environments. We conclude that the linker between the FliG N-terminal and middle domain likely adopts an extended helical conformation in vivo, in contrast with the contracted conformation observed in some previous X-ray studies. We further support our findings with integrative model building of full-length FliG and a FliG ring model that is compatible with cryo-electron tomography (cryo-ET) and electron microscopy (EM) densities of the C-ring. Collectively, our study contributes to a better mechanistic understanding of the flagellar rotor assembly and its function.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 59-67"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X22000046/pdfft?md5=54167321814b4f9235b624adb9db5f3a&pid=1-s2.0-S2665928X22000046-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45296238","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":"Super-resolution confocal cryo-CLEM with cryo-FIB milling for in situ imaging of Deinococcus radiodurans","authors":"Danielle L. Sexton ,&nbsp;Steffen Burgold ,&nbsp;Andreas Schertel ,&nbsp;Elitza I. Tocheva","doi":"10.1016/j.crstbi.2021.12.001","DOIUrl":"10.1016/j.crstbi.2021.12.001","url":null,"abstract":"<div><p>Studying bacterial cell envelope architecture with electron microscopy is challenging due to the poor preservation of microbial ultrastructure with traditional methods. Here, we established and validated a super-resolution cryo-correlative light and electron microscopy (cryo-CLEM) method, and combined it with cryo-focused ion beam (cryo-FIB) milling and scanning electron microscopy (SEM) volume imaging to structurally characterize the bacterium <em>Deinococcus radiodurans</em>. Subsequent cryo-electron tomography (cryo-ET) revealed an unusual diderm cell envelope architecture with a thick layer of peptidoglycan (PG) between the inner and outer membranes, an additional periplasmic layer, and a proteinaceous surface S-layer. Cells grew in tetrads, and division septa were formed by invagination of the inner membrane (IM), followed by a thick layer of PG. Cytoskeletal filaments, FtsA and FtsZ, were observed at the leading edges of constricting septa. Numerous macromolecular complexes were found associated with the cytoplasmic side of the IM. Altogether, our study revealed several unique ultrastructural features of <em>D. radiodurans</em> cells, opening new lines of investigation into the physiology and evolution of the bacterium.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 1-9"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39869480","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":"Engineering enhanced thermostability into the Geobacillus pallidus nitrile hydratase","authors":"Jennifer C. Van Wyk ,&nbsp;B. Trevor Sewell ,&nbsp;Michael J. Danson ,&nbsp;Tsepo L. Tsekoa ,&nbsp;Muhammed F. Sayed ,&nbsp;Don A. Cowan","doi":"10.1016/j.crstbi.2022.07.002","DOIUrl":"10.1016/j.crstbi.2022.07.002","url":null,"abstract":"<div><p>Nitrile hydratases (NHases) are important biocatalysts for the enzymatic conversion of nitriles to industrially-important amides such as acrylamide and nicotinamide. Although thermostability in this enzyme class is generally low, there is not sufficient understanding of its basis for rational enzyme design. The gene expressing the Co-type NHase from the moderate thermophile, <em>Geobacillus pallidus</em> RAPc8 (NRRL B-59396), was subjected to random mutagenesis. Four mutants were selected that were 3 to 15-fold more thermostable than the wild-type NHase, resulting in a 3.4–7.6 ​kJ/mol increase in the activation energy of thermal inactivation at 63 ​°C. High resolution X-ray crystal structures (1.15–1.80 ​Å) were obtained of the wild-type and four mutant enzymes. Mutant 9E, with a resolution of 1.15 ​Å, is the highest resolution crystal structure obtained for a nitrile hydratase to date. Structural comparisons between the wild-type and mutant enzymes illustrated the importance of salt bridges and hydrogen bonds in enhancing NHase thermostability. These additional interactions variously improved thermostability by increased intra- and inter-subunit interactions, preventing cooperative unfolding of α-helices and stabilising loop regions. Some hydrogen bonds were mediated via a water molecule, specifically highlighting the significance of structured water molecules in protein thermostability. Although knowledge of the mutant structures makes it possible to rationalize their behaviour, it would have been challenging to predict in advance that these mutants would be stabilising.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 256-270"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/5c/main.PMC9465369.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40360201","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":"Structure-based virtual screening for PDL1 dimerizers: Evaluating generic scoring functions","authors":"Viet-Khoa Tran-Nguyen ,&nbsp;Saw Simeon ,&nbsp;Muhammad Junaid ,&nbsp;Pedro J. Ballester","doi":"10.1016/j.crstbi.2022.06.002","DOIUrl":"10.1016/j.crstbi.2022.06.002","url":null,"abstract":"<div><p>The interaction between PD1 and its ligand PDL1 has been shown to render tumor cells resistant to apoptosis and promote tumor progression. An innovative mechanism to inhibit the PD1/PDL1 interaction is PDL1 dimerization induced by small-molecule PDL1 binders. Structure-based virtual screening is a promising approach to discovering such small-molecule PD1/PDL1 inhibitors. Here we investigate which type of generic scoring functions is most suitable to tackle this problem. We consider CNN-Score, an ensemble of convolutional neural networks, as the representative of machine-learning scoring functions. We also evaluate Smina, a commonly used classical scoring function, and IFP, a top structural fingerprint similarity scoring function. These three types of scoring functions were evaluated on two test sets sharing the same set of small-molecule PD1/PDL1 inhibitors, but using different types of inactives: either true inactives (molecules with no <em>in vitro</em> PD1/PDL1 inhibition activity) or assumed inactives (property-matched decoy molecules generated from each active). On both test sets, CNN-Score performed much better than Smina, which in turn strongly outperformed IFP. The fact that the latter was the case, despite precluding any possibility of exploiting decoy bias, demonstrates the predictive value of CNN-Score for PDL1. These results suggest that re-scoring Smina-docked molecules with CNN-Score is a promising structure-based virtual screening method to discover new small-molecule inhibitors of this therapeutic target.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 206-210"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40410364","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":"Crystal structure of the BREX phage defence protein BrxA","authors":"Izaak N. Beck ,&nbsp;David M. Picton ,&nbsp;Tim R. Blower","doi":"10.1016/j.crstbi.2022.06.001","DOIUrl":"10.1016/j.crstbi.2022.06.001","url":null,"abstract":"<div><p>Bacteria are constantly challenged by bacteriophage (phage) infection and have developed multitudinous and varied resistance mechanisms. Bacteriophage Exclusion (BREX) systems protect from phage infection by generating methylation patterns at non-palindromic 6 bp sites in host bacterial DNA, to distinguish and block replication of non-self DNA. Type 1 BREX systems are comprised of six conserved core genes. Here, we present the first reported structure of a BREX core protein, BrxA from the phage defence island of <em>Escherichia fergusonii</em> ATCC 35469 plasmid pEFER, solved to 2.09 ​Å. BrxA is a monomeric protein in solution, with an all α-helical globular fold. Conservation of surface charges and structural homology modelling against known phage defence systems highlighted that BrxA contains two helix-turn-helix motifs, juxtaposed by 180°, positioned to bind opposite sides of a DNA major groove. BrxA was subsequently shown to bind dsDNA. This new understanding of BrxA structure, and first indication of BrxA biological activity, suggests a conserved mode of DNA-recognition has become widespread and implemented by diverse phage defence systems.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 211-219"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40559392","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":"Metabolically-incorporated deuterium in myelin localized by neutron diffraction and identified by mass spectrometry","authors":"A. Baumann, A. Denninger, M. Domin, B. Demé, D. Kirschner","doi":"10.1101/2021.12.17.473245","DOIUrl":"https://doi.org/10.1101/2021.12.17.473245","url":null,"abstract":"Myelin is a natural and dynamic multilamellar membrane structure that continues to be of significant biological and neurological interest, especially with respect to its biosynthesis and assembly during its normal formation, maintenance, and pathological breakdown. To explore the usefulness of neutron diffraction in the structural analysis of myelin, we investigated the use of in vivo labeling by metabolically incorporating non-toxic levels of deuterium (2H; D) via drinking water into a pregnant dam (D-dam) and her developing embryos. All of the mice were sacrificed when the pups (D-pups) were 55 days old. Myelinated sciatic nerves were dissected, fixed in glutaraldehyde and examined by neutron diffraction. Parallel samples that were unfixed (trigeminal nerves) were frozen for mass spectrometry (MS). The diffraction patterns of the nerves from deuterium-fed mice (D-mice) vs. the controls (H-mice) had major differences in the intensities of the Bragg peaks but no appreciable differences in myelin periodicity. Neutron scattering density profiles showed an appreciable increase in density at the center of the lipid-rich membrane bilayer. This increase was greater in D-pups than in D-dam, and its localization was consistent with deuteration of lipid hydrocarbon, which predominates over transmembrane protein in myelin. MS analysis of the lipids isolated from the trigeminal nerves demonstrated that in the pups the percentage of lipids that had one or more deuterium atoms was uniformly high across lipid species (97.6% ± 2.0%), whereas in the mother the lipids were substantially less deuterated (60.6% ± 26.4%) with levels varying among lipid species and subspecies. The mass distribution pattern of deuterium-containing isotopologues indicated the fraction (in %) of each lipid (sub-)species having one or more deuteriums incorporated: in the D-pups, the pattern was always bell-shaped, and the average number of D atoms ranged from a low of ∼4 in fatty acid to a high of ∼9 in cerebroside. By contrast, in D-dam most lipids had more complex, overlapping distributions that were weighted toward a lower average number of deuteriums, which ranged from a low of ∼3–4 in fatty acid and in one species of sulfatide to a high of 6–7 in cerebroside and sphingomyelin. The consistently high level of deuteration in D-pups can be attributed to their de novo lipogenesis during gestation and rapid, postnatal myelination. The widely varying levels of deuteration in D-dam, by contrast, likely depends on the relative metabolic stability of the particular lipid species during myelin maintenance. Our current findings demonstrate that stably-incorporated D label can be detected and localized using neutron diffraction in a complex tissue such as myelin; and moreover, that MS can be used to screen a broad range of deuterated lipid species to monitor differential rates of lipid turnover. In addition to helping to develop a comprehensive understanding of the de novo synthesis and turnover","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 1","pages":"231 - 245"},"PeriodicalIF":2.8,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42516335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of actin cytoskeleton in the organization and function of ionotropic glutamate receptors","authors":"Priyanka Dutta ,&nbsp;Pratibha Bharti ,&nbsp;Janesh Kumar ,&nbsp;Sankar Maiti","doi":"10.1016/j.crstbi.2021.10.001","DOIUrl":"10.1016/j.crstbi.2021.10.001","url":null,"abstract":"<div><p>Neural networks with precise connection are compulsory for learning and memory. Various cellular events occur during the genesis of dendritic spines to their maturation, synapse formation, stabilization of the synapse, and proper signal transmission. The cortical actin cytoskeleton and its multiple regulatory proteins are crucial for the above cellular events. The different types of ionotropic glutamate receptors (iGluRs) present on the postsynaptic density (PSD) are also essential for learning and memory. Interaction of the iGluRs in association of their auxiliary proteins with actin cytoskeleton regulated by actin-binding proteins (ABPs) are required for precise long-term potentiation (LTP) and long-term depression (LTD). There has been a quest to understand the mechanistic detail of synapse function involving these receptors with dynamic actin cytoskeleton. A major, emerging area of investigation is the relationship between ABPs and iGluRs in synapse development. In this review we have summarized the current understanding of iGluRs functioning with respect to the actin cytoskeleton, scaffolding proteins, and their regulators. The AMPA, NMDA, Delta and Kainate receptors need the stable underlying actin cytoskeleton to anchor through synaptic proteins for precise synapse formation. The different types of ABPs present in neurons play a critical role in dynamizing/stabilizing the actin cytoskeleton needed for iGluRs function.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"3 ","pages":"Pages 277-289"},"PeriodicalIF":2.8,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/13/main.PMC8569634.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39721762","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}