In silico evolution of globular protein folds from random sequences DOI Creative Commons
Harutyun Sahakyan, S. G. Babajanyan, Yuri I. Wolf

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 10, 2024

The origin and evolution of protein folds are among the most challenging, long-standing problems in biology 1,2 . Although many plausible scenarios early leading to fold nucleation have been proposed 3-8 , realistic simulation this process was not feasible because lack efficient approaches for structure prediction, a situation that changed with advent powerful tools fast robust such as AlphaFold 9,10 ESMFold 11 We developed computational approach simulator (PFES) atomistic details provide insights into mechanisms globular from random amino acid sequences. PFES introduces mutations population sequences, evaluates effect on structure, selects new set proteins further evolution. Repeating iteratively allows tracking evolutionary trajectory changing evolves under selective pressure stability, interaction other proteins, or features shaping fitness landscape. employed show how could evolve sequences monomers complexes proteins. simulations reproduce simple natural well distinct known exist nature. stable average takes 3 8 replacements per site, suggesting but can relatively easily. These findings shed light enigma rapid diversity at earliest stages life tracks complete history describes intermediate states sequence levels be used test versatile hypotheses

Language: Английский

Diverse Mechanisms of CRISPR-Cas9 Inhibition by Type II Anti-CRISPR Proteins DOI Open Access
Sungwon Hwang, Karen L. Maxwell

Journal of Molecular Biology, Journal Year: 2023, Volume and Issue: 435(7), P. 168041 - 168041

Published: March 8, 2023

Language: Английский

Citations

19
Structural variants of AcrIIC5 inhibit Cas9 via divergent binding interfaces DOI

Sung-Hyun Hong,

So Young An,

Changkon Park

et al.

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

Published: Jan. 1, 2025

Language: Английский

Citations

0
An anti-CRISPR that represses its own transcription while blocking Cas9-target DNA binding DOI Creative Commons

Xieshuting Deng,

Wei Sun, Xueyan Li

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 28, 2024

Abstract AcrIIA15 is an anti-CRISPR (Acr) protein that inhibits Staphylococcus aureus Cas9 (SaCas9). Although previous studies suggested it has dual functions, the structural and biochemical basis for its two activities remains unclear. Here, we determined cryo-EM structure of in complex with SaCas9-sgRNA to reveal inhibitory mechanism Acr’s C-terminal domain (CTD) mimicking dsDNA block protospacer adjacent motif (PAM) recognition. For N-terminal (NTD), our crystal structures AcrIIA15-promoter DNA show dimerizes through NTD recognize double-stranded (ds) DNA. Further, can simultaneously bind both promoter DNA, creating a supercomplex Cas9s bound CTDs converging on dimer dsDNA. These findings shed light AcrIIA15’s mechanisms autoregulation transcription, enhancing understanding phage-host interactions CRISPR defense.

Language: Английский

Citations

3
A Review: CRISPR Cas System and the Mechanism With an Inhibition of Binding of CRISPR Cas‐9 DOI Creative Commons
Akram Hosen, Md Nakibul Hasan Nishat,

MD. Mohaimin Hossain Soaib

et al.

Nano Select, Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

ABSTRACT CRISPR Cas system is a revolutionary and precise genome editing that induces bacterial archaeal adaptive immunity already has shown several promising applications in the treatment of genetic diseases detection nucleic acid targets. It complex tool, comprising diverse effector proteins guide RNA can be applied to dissociate modify genes living organisms along with vitro process. The review concentrates on advances accomplished from some recent years 2023 for emergence predicting actions protein (gRNA), playing key role editing. This emphasizes effect DNA structure chromosomal 9 binding distinct classification types. relevance this highlighted by significance rapid development wide study methods their potential impacts efficiency system. We have analyzed kinds literature work integrate deep learning way contributes over next time important discussion about viral resistance eukaryotes cancer strategies, crop improvement

Language: Английский

Citations

1
Inhibitory mechanism of CRISPR-Cas9 by AcrIIC4 DOI Creative Commons
Xuzichao Li,

Fumeng Liao,

Jiaqi Gao

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(17), P. 9442 - 9451

Published: Aug. 12, 2023

CRISPR-Cas systems act as the adaptive immune of bacteria and archaea, targeting destroying invading foreign mobile genetic elements (MGEs) such phages. MGEs have also evolved anti-CRISPR (Acr) proteins to inactivate systems. Recently, AcrIIC4, identified from Haemophilus parainfluenzae phage, has been reported inhibit endonuclease activity Cas9 Neisseria meningitidis (NmeCas9), but inhibition mechanism is not clear. Here, we biochemically structurally investigated AcrIIC4. AcrIIC4 folds into a helix bundle composed three helices, which associates with REC lobe NmeCas9 sgRNA. The REC2 domain locked by perturbing conformational dynamics required for target DNA binding cleavage. Furthermore, mutation key residues in AcrIIC4-NmeCas9 AcrIIC4-sgRNA interfaces largely abolishes inhibitory effects Our study offers new insights AcrIIC4-mediated suppression provides guidelines design regulatory tools Cas9-based gene editing applications.

Language: Английский

Citations

2
Ten Years of Anti-CRISPR Research DOI Open Access
Joseph Bondy‐Denomy, Karen L. Maxwell, Alan R. Davidson

et al.

Journal of Molecular Biology, Journal Year: 2023, Volume and Issue: 435(7), P. 168058 - 168058

Published: March 22, 2023

Language: Английский

Citations

1
In silico evolution of globular protein folds from random sequences DOI Creative Commons
Harutyun Sahakyan, S. G. Babajanyan, Yuri I. Wolf

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 10, 2024

The origin and evolution of protein folds are among the most challenging, long-standing problems in biology 1,2 . Although many plausible scenarios early leading to fold nucleation have been proposed 3-8 , realistic simulation this process was not feasible because lack efficient approaches for structure prediction, a situation that changed with advent powerful tools fast robust such as AlphaFold 9,10 ESMFold 11 We developed computational approach simulator (PFES) atomistic details provide insights into mechanisms globular from random amino acid sequences. PFES introduces mutations population sequences, evaluates effect on structure, selects new set proteins further evolution. Repeating iteratively allows tracking evolutionary trajectory changing evolves under selective pressure stability, interaction other proteins, or features shaping fitness landscape. employed show how could evolve sequences monomers complexes proteins. simulations reproduce simple natural well distinct known exist nature. stable average takes 3 8 replacements per site, suggesting but can relatively easily. These findings shed light enigma rapid diversity at earliest stages life tracks complete history describes intermediate states sequence levels be used test versatile hypotheses

Language: Английский

Citations

0