Cited by The molecular architecture of the nuclear basket

Translation dynamics in human cells visualized at high resolution reveal cancer drug action DOI

Huaipeng Xing, Reiya Taniguchi, Iskander Khusainov

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6653), P. 70 - 75

Published: July 6, 2023

Ribosomes catalyze protein synthesis by cycling through various functional states. These states have been extensively characterized in vitro, but their distribution actively translating human cells remains elusive. We used a cryo-electron tomography-based approach and resolved ribosome structures inside with high resolution. revealed the of elongation cycle, Z transfer RNA binding site, dynamics expansion segments. Ribosome from treated Homoharringtonine, drug against chronic myeloid leukemia, how translation were altered situ resolve small molecules within active site ribosome. Thus, structural effects can be assessed at resolution cells.

Language: Английский

Citations

Nuclear transport proteins: structure, function, and disease relevance DOI

Yang Yang,

Lu Guo,

Lin Chen

et al.

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

Published: Nov. 10, 2023

Abstract Proper subcellular localization is crucial for the functioning of biomacromolecules, including proteins and RNAs. Nuclear transport a fundamental cellular process that regulates many macromolecules within nuclear or cytoplasmic compartments. In humans, approximately 60 are involved in transport, nucleoporins form membrane-embedded pore complexes, karyopherins cargoes through these Ran system ensure directed rapid transport. Many play additional essential roles mitosis, biomolecular condensation, gene transcription. Dysregulation linked to major human diseases such as cancer, neurodegenerative diseases, viral infections. Selinexor (KPT-330), an inhibitor targeting export factor XPO1 (also known CRM1), was approved 2019 treat two types blood cancers, dozens clinical trials ongoing. This review summarizes three decades research data this field but focuses on structure function individual from recent studies, providing cutting-edge holistic view role health disease. In-depth knowledge rapidly evolving has potential bring new insights into biology, pathogenic mechanisms, therapeutic approaches.

Language: Английский

Citations

AlphaFold2 protein structure prediction: Implications for drug discovery DOI

Neera Borkakoti, Janet M. Thornton

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 78, P. 102526 - 102526

Published: Jan. 6, 2023

Language: Английский

Citations

Cryo-electron tomography on focused ion beam lamellae transforms structural cell biology DOI

Casper Berger,

Navya Premaraj,

Raimond B. G. Ravelli

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 20(4), P. 499 - 511

Published: March 13, 2023

Language: Английский

Citations

Bridging structural and cell biology with cryo-electron microscopy DOI

Eva Nogales, Julia Mahamid

Nature, Journal Year: 2024, Volume and Issue: 628(8006), P. 47 - 56

Published: April 3, 2024

Language: Английский

Citations

AlphaFold2 structures guide prospective ligand discovery DOI

Jiankun Lyu, Nicholas J. Kapolka, Ryan H. Gumpper

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6702)

Published: May 16, 2024

AlphaFold2 (AF2) models have had wide impact but mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 of the σ

Language: Английский

Citations

TomoTwin: generalized 3D localization of macromolecules in cryo-electron tomograms with structural data mining DOI

Gavin Rice, Thorsten Wagner, Markus Stabrin

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 20(6), P. 871 - 880

Published: May 15, 2023

Cryogenic-electron tomography enables the visualization of cellular environments in extreme detail, however, tools to analyze full amount information contained within these densely packed volumes are still needed. Detailed analysis macromolecules through subtomogram averaging requires particles first be localized tomogram volume, a task complicated by several factors including low signal noise ratio and crowding space. Available methods for this suffer either from being error prone or requiring manual annotation training data. To assist crucial particle picking step, we present TomoTwin: an open source general model cryogenic-electron tomograms based on deep metric learning. By embedding information-rich, high-dimensional space that separates according their three-dimensional structure, TomoTwin allows users identify proteins de novo without manually creating data retraining network locate new proteins.

Language: Английский

Citations

HIV-1 capsids enter the FG phase of nuclear pores like a transport receptor DOI

Liran Fu, Erika N. Weiskopf, Onno Akkermans

et al.

Nature, Journal Year: 2024, Volume and Issue: 626(8000), P. 843 - 851

Published: Jan. 24, 2024

Abstract HIV-1 infection requires nuclear entry of the viral genome. Previous evidence suggests that this proceeds through pore complexes (NPCs), with 120 × 60 nm capsid squeezing an approximately 60-nm-wide central channel 1 and crossing permeability barrier NPC. This can be described as FG phase 2 is assembled from cohesively interacting phenylalanine–glycine (FG) repeats 3 selectively permeable to cargo captured by transport receptors (NTRs). Here we show assemblies target NPCs efficiently in NTR-independent manner bind directly several types repeats, including barrier-forming cohesive repeats. Like NTRs, readily partitions into vitro serve NPC mimic excludes much smaller inert probes such mCherry. Indeed, protein greatly enhanced assembly, which also allows encapsulated clients enter. Thus, our data indicate behaves like NTR, its interior serving a container. Because capsid-coating trans -acting NTRs would increase diameter 10 or more, suggest ‘self-translocating’ undermines size restrictions imposed scaffold, thereby bypassing otherwise effective infection.

Language: Английский

Citations

A quantitative map of nuclear pore assembly reveals two distinct mechanisms DOI

Shotaro Otsuka, Jeremy O. B. Tempkin, Wanlu Zhang

et al.

Nature, Journal Year: 2023, Volume and Issue: 613(7944), P. 575 - 581

Published: Jan. 4, 2023

Understanding how the nuclear pore complex (NPC) is assembled of fundamental importance to grasp mechanisms behind its essential function and understand role during evolution eukaryotes

Language: Английский

Citations

Pragmatic Coarse-Graining of Proteins: Models and Applications DOI

Luís Borges-Araújo, Ilias Patmanidis, Akhil Pratap Singh

et al.

Journal of Chemical Theory and Computation, Journal Year: 2023, Volume and Issue: 19(20), P. 7112 - 7135

Published: Oct. 3, 2023

The molecular details involved in the folding, dynamics, organization, and interaction of proteins with other molecules are often difficult to assess by experimental techniques. Consequently, computational models play an ever-increasing role field. However, biological processes involving large-scale protein assemblies or long time scale dynamics still computationally expensive study atomistic detail. For these applications, employing coarse-grained (CG) modeling approaches has become a key strategy. In this Review, we provide overview what call pragmatic CG models, which strategies combining, at least part, physics-based implementation top-down approach their parametrization. particular, focus on most residues represented two beads, allowing retain some degree chemical specificity. A description main modern is provided, including review recent applications outlook future perspectives

Language: Английский

Citations