QRB Discovery最新文献_第4页

Filling in missing puzzle pieces in protein structural biology with cross-linking mass spectrometry. 用交联质谱法填补蛋白质结构生物学中缺失的拼图。

QRB Discovery Pub Date : 2024-12-27 eCollection Date: 2025-01-01 DOI: 10.1017/qrd.2024.13

Zheng Ser

{"title":"Filling in missing puzzle pieces in protein structural biology with cross-linking mass spectrometry.","authors":"Zheng Ser","doi":"10.1017/qrd.2024.13","DOIUrl":"10.1017/qrd.2024.13","url":null,"abstract":"High resolution structures of protein complexes provide a wealth of information on protein structure and function. Databases of these protein structures are also used for artificial-intelligence (AI)-based methods of structural modelling. Despite the wealth of protein structures that have been determined by structural biologists, there are still gaps, or missing pieces in the puzzle of protein structural biology. Highly flexible regions may be missing from protein structures and conformational changes of different protein complex states may not be captured by current databases. In this perspective, I sketch out several ways that cross-linking mass spectrometry can contribute to filling in some of these missing pieces: Identification of cross-linked interactions in highly flexible protein regions not captured by other structural techniques; capturing conformational changes of protein complexes in different functional states; serving as distance constraints in integrative structural modelling and providing structural information of in cellulo proteins. The myriad ways in which cross-linking mass spectrometry contributes to filling in missing pieces in structural biology makes it a powerful technique in structural biology.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"6 ","pages":"e6"},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754851","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}

引用次数: 0

Calcium-binding site in AA10 LPMO from Vibrio cholerae suggests modulating effects during environmental survival and infection. 霍乱弧菌AA10 LPMO中的钙结合位点提示在环境存活和感染过程中具有调节作用。

QRB Discovery Pub Date : 2024-12-26 eCollection Date: 2024-01-01 DOI: 10.1017/qrd.2024.14

Mateu Montserrat-Canals, Kaare Bjerregaard-Andersen, Henrik Vinther Sørensen, Eirik Kommedal, Gabriele Cordara, Gustav Vaaje-Kolstad, Ute Krengel

{"title":"Calcium-binding site in AA10 LPMO from Vibrio cholerae suggests modulating effects during environmental survival and infection.","authors":"Mateu Montserrat-Canals, Kaare Bjerregaard-Andersen, Henrik Vinther Sørensen, Eirik Kommedal, Gabriele Cordara, Gustav Vaaje-Kolstad, Ute Krengel","doi":"10.1017/qrd.2024.14","DOIUrl":"10.1017/qrd.2024.14","url":null,"abstract":"Despite major efforts toward its eradication, cholera remains a major health threat and economic burden in many low- and middle-income countries. Between outbreaks, the bacterium responsible for the disease, Vibrio cholerae, survives in aquatic environmental reservoirs, where it commonly forms biofilms, for example, on zooplankton. N-acetyl glucosamine-binding protein A (GbpA) is an adhesin that binds to the chitinaceous surface of zooplankton and breaks its dense crystalline packing thanks to its lytic polysaccharide monooxygenase (LPMO) activity, which provides V. cholerae with nutrients. In addition, GbpA is an important colonization factor associated with bacterial pathogenicity, allowing the binding to mucins in the host intestine. Here, we report the discovery of a cation-binding site in proximity of the GbpA active site, which allows Ca2+, Mg2+, or K+ binding close to its carbohydrate-binding surface. In addition to the X-ray crystal structures of cation-LPMO complexes (to 1.5 Å resolution), we explored how the presence of ions affects the stability and activity of the protein. Calcium and magnesium ions were found to bind to GbpA specifically, with calcium ions - abundant in natural sources of chitin - having the strongest effect on protein stability. When the cation-binding site was rendered non-functional, a decrease in activity was observed, highlighting the importance of the structural elements stabilized by calcium. Our findings suggest a cation-binding site specific to GbpA and related LPMOs that may fine-tune binding and activity for its substrates during environmental survival and host infection.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"5 ","pages":"e12"},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984103","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}

引用次数: 0

An integrated approach using proximity labelling and chemical crosslinking to probe in situ host-virus protein-protein interactions. 使用接近标记和化学交联的综合方法来原位探测宿主-病毒蛋白质-蛋白质相互作用。

QRB Discovery Pub Date : 2024-12-16 eCollection Date: 2024-01-01 DOI: 10.1017/qrd.2024.19

Jiaqi Li, Zhewang Lin

引用次数: 0

The conformational landscape of TRiC ring-opening and its underlying stepwise mechanism revealed by cryo-EM. 低温电子显微镜揭示了TRiC开环的构象景观及其潜在的逐步机理。

QRB Discovery Pub Date : 2024-12-16 eCollection Date: 2025-01-01 DOI: 10.1017/qrd.2024.17

Mingliang Jin, Yunxiang Zang, Huping Wang, Yao Cong

{"title":"The conformational landscape of TRiC ring-opening and its underlying stepwise mechanism revealed by cryo-EM.","authors":"Mingliang Jin, Yunxiang Zang, Huping Wang, Yao Cong","doi":"10.1017/qrd.2024.17","DOIUrl":"10.1017/qrd.2024.17","url":null,"abstract":"The TRiC/CCT complex assists in the folding of approximately 10% of cytosolic proteins through an ATP-driven conformational cycle, playing a crucial role in maintaining protein homeostasis. Despite our understanding of ATP-driven TRiC ring closing and substrate folding, the process and mechanisms underlying TRiC ring-opening and substrate release remain largely unexplored. In this study, by determining an ensemble of cryo-EM structures of yeast TRiC in the presence of ADP, including three intermediate transition states, we present a comprehensive picture of the TRiC ring-opening process. During this process, CCT3 detects the loss of γ-phosphate and initiates with the dynamics of its apical protrusion, and expands to the outward leaning of the consecutive CCT6/8/7/5 subunits. This is followed by significant movements of CCT2, CCT4, and especially CCT1 subunits, resulting in the opening of the TRiC rings. We also observed an unforeseen temporary separation between the two rings in the CCT2 side, coordinating the release of the originally locked CCT4 N-terminus, which potentially participates in the ring-opening process. Collectively, our study reveals a stepwise TRiC ring-opening mechanism, provides a comprehensive view of the TRiC conformational landscape, and sheds lights on its subunit specificity in sensing nucleotide status and substrate release. Our findings deepen our understanding of protein folding assisted by TRiC and may inspire new strategies for the diagnosis and treatment of related diseases.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"6 ","pages":"e7"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606391","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}

引用次数: 0

The big chill: Growth of in situ structural biology with cryo-electron tomography. 大寒意：低温电子断层扫描原位结构生物学的生长。

QRB Discovery Pub Date : 2024-12-13 eCollection Date: 2024-01-01 DOI: 10.1017/qrd.2024.10

Mikhail Kudryashev

引用次数: 0

Structural bioinformatic study of six human olfactory receptors and their AlphaFold3 predicted water-soluble QTY variants and OR1A2 with an odorant octanoate and TAAR9 with spermidine. 六种人类嗅觉受体及其AlphaFold3的结构生物信息学研究预测了水溶性QTY变异，OR1A2预测了气味辛酸盐，TAAR9预测了亚精胺。

QRB Discovery Pub Date : 2024-12-09 eCollection Date: 2025-01-01 DOI: 10.1017/qrd.2024.18

Finn Johnsson, Taner Karagöl, Alper Karagöl, Shuguang Zhang

{"title":"Structural bioinformatic study of six human olfactory receptors and their AlphaFold3 predicted water-soluble QTY variants and OR1A2 with an odorant octanoate and TAAR9 with spermidine.","authors":"Finn Johnsson, Taner Karagöl, Alper Karagöl, Shuguang Zhang","doi":"10.1017/qrd.2024.18","DOIUrl":"10.1017/qrd.2024.18","url":null,"abstract":"The molecular mechanism of olfaction, namely, how we smell with limited olfactory receptors to recognize exceedingly diverse and large numbers of scents remains unknown despite the recent advances in chemistry, chemical, structural, and molecular biology. Olfactory receptors are notoriously difficult to study because they are fully embedded in the cell membrane. After decades of efforts and significant funding, there are only three olfactory receptor structures known. To understand olfaction, we carried out the structural bioinformatic study of six human olfactory receptors including OR51E1, OR51E2, OR52cs, OR1A1, OR1A2, TAAR9, and their AlphaFold3 predicted water-soluble QTY variants with odorants. We applied the QTY code to replace leucine (L) with glutamine (Q), isoleucine (I) and valine (V) with threonine (T), and phenylalanine (F) with tyrosine (Y) only in the transmembrane helices. Therefore, these QTY variants become water-soluble. We also present the superimposed structures of native olfactory receptors and their water-soluble QTY variants. The superimposed structures show remarkable similarity with RMSDs between 0.441 and 1.275 Å despite significant changes to the protein sequence of the transmembrane domains (43.03%-50.31%). We also show the differences in hydrophobicity surfaces between the native olfactory receptors and their QTY variants. Furthermore, we also used AlphaFold3 and molecular dynamics to study the odorant octanoate with OR1A2 and spermidine with TAAR9. Our bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices, and will likely further stimulate designs of water-soluble integral transmembrane proteins and other aggregated proteins.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"6 ","pages":"e2"},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410463","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}

引用次数: 0

Handheld portable device for delivering capped silver nanoparticles for antimicrobial applications. 手持式便携式设备，用于提供用于抗菌应用的盖银纳米颗粒。

QRB Discovery Pub Date : 2024-12-03 eCollection Date: 2024-01-01 DOI: 10.1017/qrd.2024.9

Kumar Naveen, Sandeep Bose, Chanbasha Basheer, Richard N Zare, Elumalai Gnanamani

{"title":"Handheld portable device for delivering capped silver nanoparticles for antimicrobial applications.","authors":"Kumar Naveen, Sandeep Bose, Chanbasha Basheer, Richard N Zare, Elumalai Gnanamani","doi":"10.1017/qrd.2024.9","DOIUrl":"10.1017/qrd.2024.9","url":null,"abstract":"We describe a simple, cost-effective, green method for producing capped silver nanoparticles (Ag NPs) using a handheld portable mesh nebulizer. The precursor solution containing a 1:1 mixture of silver nitrate (AgNO3) and ligand (glycerol or sodium alginate) was sprayed using the nebulizer. The Ag NPs were generated in the water microdroplets within a few milliseconds under ambient conditions without any external reducing agent or action of a radiation source. The synthesized nanoparticles were characterized by using high-resolution transmission electron microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction analysis (XRD), which validated the formation of Ag NPs. The synthesized glycerate-capped silver nanoparticles (Ag-gly NPs) were used as a catalyst to show the oxidative coupling of aniline to form azobenzene products with a yield of up to 61%. Experiments conducted using Ag NPs produced in the droplets demonstrated more than 99% antibacterial activity when contacting Escherichia Coli. Our in-situ synthesis-cum-fabrication technique using a portable sprayer represents a viable alternative to the existing fiber or hydrogel-based antimicrobial wound healing.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"5 ","pages":"e9"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839843","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}

引用次数: 0

The potential of fluorogenicity for single molecule FRET and DyeCycling. 单分子FRET和染料循环的致氟性潜力。

QRB Discovery Pub Date : 2024-12-03 eCollection Date: 2024-01-01 DOI: 10.1017/qrd.2024.11

Srijayee Ghosh, Sonja Schmid

{"title":"The potential of fluorogenicity for single molecule FRET and DyeCycling.","authors":"Srijayee Ghosh, Sonja Schmid","doi":"10.1017/qrd.2024.11","DOIUrl":"10.1017/qrd.2024.11","url":null,"abstract":"Single Molecule Förster Resonance Energy Transfer (smFRET) is a popular technique to directly observe biomolecular dynamics in real time, offering unique mechanistic insight into proteins, ribozymes, and so forth. However, inevitable photobleaching of the fluorophores puts a stringent limit on the total time a surface-tethered molecule can be monitored, fundamentally limiting the information gain through conventional smFRET measurements. DyeCycling addresses this problem by using reversibly - instead of covalently - coupled FRET fluorophores, through which it can break the photobleaching limit and theoretically provide unlimited observation time. In this perspective paper, we discuss the potential of various fluorogenic strategies to suppress the background fluorescence caused by unbound, freely diffusing fluorophores inherent to the DyeCycling approach. In comparison to nanophotonic background suppression using zero-mode waveguides, the fluorogenic approach would enable DyeCycling experiments on regular glass slides with fluorogenic FRET probes that are quenched in solution and only fluoresce upon target binding. We review a number of fluorogenic approaches and conclude, among other things, that short-range quenching appears promising for realising fluorogenic DyeCycling on regular glass slides. We anticipate that our discussion will be relevant for all single-molecule fluorescence techniques that use reversible fluorophore binding.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"5 ","pages":"e8"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839862","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}

引用次数: 0

The Future of Chemistry is through Computations. 化学的未来在于计算。

QRB Discovery Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.1017/qrd.2024.16

Giulia Palermo, Bengt Nordén

引用次数: 0

As air relative humidity increases, infectivity of SARS-CoV-2 decreases within water droplets. 随着空气相对湿度的增加，SARS-CoV-2在水滴中的传染性降低。

QRB Discovery Pub Date : 2024-08-29 eCollection Date: 2024-01-01 DOI: 10.1017/qrd.2024.7

Yu Liu, Lei Cao, Yu Xia, Pan Pan, Lang Rao, Bolei Chen, Richard N Zare

引用次数: 0