Ring-stacked capsids of white spot syndrome virus and structural transitions with genome ejection DOI Creative Commons
Meiling Sun, Mingdong Liu, Hong Shan

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(8)

Published: Feb. 22, 2023

White spot syndrome virus (WSSV) is one of the largest DNA viruses and major pathogen responsible for white in crustaceans. The WSSV capsid critical genome encapsulation ejection exhibits rod-shaped oval-shaped structures during viral life cycle. However, detailed architecture structural transition mechanism remain unclear. Here, using cryo-electron microscopy (cryo-EM), we obtained a cryo-EM model were able to characterize its ring-stacked assembly mechanism. Furthermore, identified an from intact virions analyzed capsids induced by high salinity. These transitions, which decrease internal pressure, always accompany release mostly eliminate infection host cells. Our results demonstrate unusual offer insights into pressure-driven release.

Language: Английский

AlphaFold2 and its applications in the fields of biology and medicine DOI Creative Commons
Zhenyu Yang, Xiaoxi Zeng, Yi Zhao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 14, 2023

Abstract AlphaFold2 (AF2) is an artificial intelligence (AI) system developed by DeepMind that can predict three-dimensional (3D) structures of proteins from amino acid sequences with atomic-level accuracy. Protein structure prediction one the most challenging problems in computational biology and chemistry, has puzzled scientists for 50 years. The advent AF2 presents unprecedented progress protein attracted much attention. Subsequent release more than 200 million predicted further aroused great enthusiasm science community, especially fields medicine. thought to have a significant impact on structural research areas need information, such as drug discovery, design, function, et al. Though time not long since was developed, there are already quite few application studies medicine, many them having preliminarily proved potential AF2. To better understand promote its applications, we will this article summarize principle architecture well recipe success, particularly focus reviewing applications Limitations current also be discussed.

Language: Английский

Citations

256
Automated model building and protein identification in cryo-EM maps DOI Creative Commons
Kiarash Jamali, Lukas Käll, Rui Zhang

et al.

Nature, Journal Year: 2024, Volume and Issue: 628(8007), P. 450 - 457

Published: Feb. 26, 2024

Interpreting electron cryo-microscopy (cryo-EM) maps with atomic models requires high levels of expertise and labour-intensive manual intervention in three-dimensional computer graphics programs

Language: Английский

Citations

249
Structural specializations of the sperm tail DOI Creative Commons
Miguel Ricardo Leung, Jianwei Zeng, Xiangli Wang

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(13), P. 2880 - 2896.e17

Published: June 1, 2023

Sperm motility is crucial to reproductive success in sexually reproducing organisms. Impaired sperm movement causes male infertility, which increasing globally. are powered by a microtubule-based molecular machine—the axoneme—but it unclear how axonemal microtubules ornamented support diverse fertilization environments. Here, we present high-resolution structures of native doublet (DMTs) from sea urchin and bovine sperm, representing external internal fertilizers. We identify >60 proteins decorating DMTs; at least 15 associated 16 linked infertility. By comparing DMTs across species cell types, define core microtubule inner (MIPs) analyze evolution the tektin bundle. conserved microtubule-associated (MAPs) with unique tubulin-binding modes. Additionally, testis-specific serine/threonine kinase that links outer dense fibers mammalian sperm. Our study provides structural foundations for understanding evolution, motility, dysfunction level.

Language: Английский

Citations

82
Automated model building and protein identification in cryo-EM maps DOI Creative Commons
Kiarash Jamali, Lukas Käll, Rui Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 16, 2023

Interpreting electron cryo-microscopy (cryo-EM) maps with atomic models requires high levels of expertise and labour-intensive manual intervention. We present ModelAngelo, a machine-learning approach for automated model building in cryo-EM maps. By combining information from the map protein sequence structure single graph neural network, ModelAngelo builds proteins that are similar quality as those generated by human experts. For nucleotides, backbones accuracy humans. using its predicted amino acid probabilities each residue hidden Markov searches, outperforms experts identification unknown sequences. will thus remove bottlenecks increase objectivity determination.

Language: Английский

Citations

75
Integrating cellular electron microscopy with multimodal data to explore biology across space and time DOI Creative Commons
Caitlyn L McCafferty, Sven Klumpe, Rommie E. Amaro

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 563 - 584

Published: Feb. 1, 2024

Biology spans a continuum of length and time scales. Individual experimental methods only glimpse discrete pieces this spectrum but can be combined to construct more holistic view. In Review, we detail the latest advancements in volume electron microscopy (vEM) cryo-electron tomography (cryo-ET), which together visualize biological complexity across scales from organization cells large tissues molecular details inside native cellular environments. addition, discuss emerging methodologies for integrating three-dimensional (3DEM) imaging with multimodal data, including fluorescence microscopy, mass spectrometry, single-particle analysis, AI-based structure prediction. This multifaceted approach fills gaps continuum, providing functional context, spatial organization, identity, interactions. We conclude perspective on incorporating diverse data into computational simulations that further bridge extend while dimension time.

Language: Английский

Citations

45
Structural diversity of axonemes across mammalian motile cilia DOI Creative Commons
Miguel Ricardo Leung, Chen Sun, Jianwei Zeng

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of axoneme available for alga Chlamydomonas reinhardtii 1 , structures mammalian axonemes are incomplete 1–5 . Furthermore, we do not fully understand how vary across motile-ciliated cell types in body. Here use cryoelectron microscopy, tomography proteomics to resolve 96-nm modular repeat axonemal doublet microtubules (DMTs) from both sperm flagella epithelial cilia oviduct, brain ventricles respiratory tract. We find that DMTs most specialized, with having only minor differences tissues. build DMT, defining positions interactions 181 proteins including 34 newly identified proteins. elucidate composition radial spoke 3 uncover binding sites kinases associated regeneration ATP regulation ciliary motility. discover sperm-specific, axoneme-tethered T-complex protein ring complex (TRiC) chaperone may contribute construction or maintenance long sperm. dyneins their prestroke states, illuminating conformational changes occur during movement. Our results illustrate elements chemical mechanical embedded within axoneme, providing valuable resources understanding aetiology ciliopathy infertility, exemplifying discovery power modern structural biology.

Language: Английский

Citations

6
Extracellular cytochrome nanowires appear to be ubiquitous in prokaryotes DOI Creative Commons
Diana P. Baquero, Virginija Cvirkaitė‐Krupovič, Shengen Hu

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(13), P. 2853 - 2864.e8

Published: June 1, 2023

Language: Английский

Citations

43
Deep learning for reconstructing protein structures from cryo-EM density maps: Recent advances and future directions DOI Creative Commons
Nabin Giri, Raj S. Roy, Jianlin Cheng

et al.

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 79, P. 102536 - 102536

Published: Feb. 9, 2023

Cryo-Electron Microscopy (cryo-EM) has emerged as a key technology to determine the structure of proteins, particularly large protein complexes and assemblies in recent years. A challenge cryo-EM data analysis is automatically reconstruct accurate structures from density maps. In this review, we briefly overview various deep learning methods for building maps, analyze their impact, discuss challenges preparing high-quality sets training models. Looking into future, more advanced models effectively integrating with other sources complementary such sequences AlphaFold-predicted need be developed further advance field.

Language: Английский

Citations

41
Does AlphaFold2 model proteins’ intracellular conformations? An experimental test using cross-linking mass spectrometry of endogenous ciliary proteins DOI Creative Commons
Caitlyn L McCafferty, Erin L. Pennington, Ophelia Papoulas

et al.

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: April 15, 2023

A major goal in structural biology is to understand protein assemblies their biologically relevant states. Here, we investigate whether AlphaFold2 structure predictions match native conformations. We chemically cross-linked proteins situ within intact Tetrahymena thermophila cilia and ciliary extracts, identifying 1,225 intramolecular cross-links the 100 best-sampled proteins, providing a benchmark of distance restraints obeyed by assemblies. The corresponding were highly concordant, positioning 86.2% residues Cɑ-to-Cɑ distances 30 Å, consistent with cross-linker length. 43% showed no violations. Most inconsistencies occurred low-confidence regions or between domains. Overall, lower predicted aligned error corresponded more correct structures. However, observe cases where rigid body domains are oriented incorrectly, as for BBC118, suggesting that combining prediction experimental information will better reveal

Language: Английский

Citations

25
Improving Protein–Ligand Interaction Modeling with cryo-EM Data, Templates, and Deep Learning in 2021 Ligand Model Challenge DOI Creative Commons
Nabin Giri, Jianlin Cheng

Biomolecules, Journal Year: 2023, Volume and Issue: 13(1), P. 132 - 132

Published: Jan. 9, 2023

Elucidating protein–ligand interaction is crucial for studying the function of proteins and compounds in an organism critical drug discovery design. The problem traditionally tackled by molecular docking simulation, which based on physical forces statistical potentials cannot effectively leverage cryo-EM data existing protein structural information modeling process. In this work, we developed a deep learning bioinformatics pipeline (DeepProLigand) to predict interactions from density maps ligands. DeepProLigand first uses method structure maps, averaged with reference (template) produce combined add ligands are then identified added into generate complex structure, further refined. prediction template-based was blindly tested 2021 EMDataResource Ligand Challenge ranked fitting maps. These results demonstrate that approach promising direction using prior information.

Language: Английский

Citations

20