Fast and scalable querying of eukaryotic linear motifs withgget elm DOI Creative Commons
Laura Luebbert, Chi Linh Hoang, Manjeet Kumar

et al.

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

Published: Nov. 17, 2023

Abstract Motivation Eukaryotic linear motifs (ELMs), or Short Linear Motifs (SLiMs), are protein interaction modules that play an essential role in cellular processes and signaling networks often involved diseases like cancer. The ELM database is a collection of manually curated motif knowledge from scientific papers. It has become crucial resource for cataloging biology recognizing candidate ELMs novel amino acid sequences. Users can search sequences UniProt IDs on the web interface. However, as with many services, there limitations swift processing large-scale queries through interface API calls, and, therefore, integration into function analysis pipelines limited. Results To allow swift, analyses using database, we have developed Python command line tool, gget elm , which relies local computations efficiently finding user-submitted identifiers. increases accessibility to information stored allows scalable searches motif-mediated sites Availability implementation manual source code available at https://github.com/pachterlab/gget .

Language: Английский

The molecular basis for cellular function of intrinsically disordered protein regions DOI
Alex S. Holehouse, Birthe B. Kragelund

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 187 - 211

Published: Nov. 13, 2023

Language: Английский

Citations

235
Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs DOI Creative Commons
Filip Mihalič, Leandro Simonetti, Girolamo Giudice

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 26, 2023

Viruses mimic host short linear motifs (SLiMs) to hijack and deregulate cellular functions. Studies of motif-mediated interactions therefore provide insight into virus-host dependencies, reveal targets for therapeutic intervention. Here, we describe the pan-viral discovery 1712 SLiM-based using a phage peptidome tiling intrinsically disordered protein regions 229 RNA viruses. We find mimicry SLiMs be ubiquitous viral strategy, novel proteins hijacked by viruses, identify pathways frequently deregulated motif mimicry. Using structural biophysical analyses, show that mimicry-based have similar binding strength bound conformations as endogenous interactions. Finally, establish polyadenylate-binding 1 potential target broad-spectrum antiviral agent development. Our platform enables rapid mechanisms interference identification which can aid in combating future epidemics pandemics.

Language: Английский

Citations

34
The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions DOI Creative Commons

Dimitriya H. Garvanska,

R. Elias Alvarado, Filip Mundt

et al.

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(2), P. 902 - 926

Published: Jan. 2, 2024

Language: Английский

Citations

10
Proteome-scale characterisation of motif-based interactome rewiring by disease mutations DOI Creative Commons
Johanna Kliche, Leandro Simonetti, Izabella Krystkowiak

et al.

Molecular Systems Biology, Journal Year: 2024, Volume and Issue: 20(9), P. 1025 - 1048

Published: July 15, 2024

Language: Английский

Citations

4
Cell signaling in Ehrlichia infection and cancer: Parallels in pathogenesis DOI Creative Commons
Regina N. Solomon,

Nicholas A. Pittner,

James McCoy

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 14, 2025

Ehrlichia chaffeensis ( E. ) has recently emerged as an intracellular bacterial pathogen with sophisticated survival mechanisms that include repurposing evolutionarily conserved eukaryotic cell signaling pathways for immune evasion. exploits four major developmental (Wnt, Notch, Hedgehog, and Hippo) using s hort li near m otif (SLiM) ligand mimicry to initiate cascades. Dysregulation of these leading unchecked is implicated in various diseases, most notably cancer. Wnt, Hedgehog Hippo inhibit apoptosis co-opt other cellular functions promote infection. This review will explore the exploited during infection new discoveries have illuminated this interesting example convergence cancer biology.

Language: Английский

Citations

0
Deep learning in the discovery of antiviral peptides and peptidomimetics: databases and prediction tools DOI
Maryam Nawaz,

Yao Huiyuan,

Fahad Akhtar

et al.

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Language: Английский

Citations

0
A chemical-genetic system to rapidly inhibit the PP2A-B56 phosphatase reveals a role at metaphase kinetochores DOI Creative Commons
Lindsey A Allan, Andrea Corno, Juan Manuel Valverde

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 29, 2025

Abstract Serine-threonine phosphatases have been challenging to study because of the lack specific inhibitors. Their catalytic domains are druggable, but these shared or very similar between individual phosphatase complexes, precluding their inhibition. Instead, complexes often achieve specificity by interacting with short linear motifs (SLiMs) in substrates binding partners. We develop here a chemical-genetic system rapidly inhibit interactions within PP2A-B56 family. Drug-inducible recruitment ectopic SLiMs (“directSLiMs”) is used block SLiM-binding pocket on B56 regulatory subunit, thereby displacing endogenous interactors and inhibiting activity seconds. use this characterise during mitosis identify role for allowing metaphase kinetochores properly sense tension maintain microtubule attachments. The directSLiMs approach can be any other phosphatase, enzyme protein that uses critical interface, providing powerful strategy proteins once considered “undruggable”.

Language: Английский

Citations

0
Diversity of short linear interaction motifs in SARS-CoV-2 nucleocapsid protein DOI Creative Commons
Peter Schuck, Huaying Zhao

mBio, Journal Year: 2023, Volume and Issue: 14(6)

Published: Nov. 29, 2023

ABSTRACT Molecular mimicry of short linear interaction motifs has emerged as a key mechanism for viral proteins binding host domains and hijacking cell processes. Here, we examine the role RNA virus sequence diversity in dynamics virus-host interface by analyzing uniquely vast record viable SARS-CoV-2 species with focus on multi-functional nucleocapsid protein. We observe abundant presentation encoding several essential protein interactions, alongside majority possibly non-functional randomly occurring motif sequences absent subsets species. A large number emerge ex nihilo through transient mutations relative to ancestral consensus sequence. The observed mutational landscape implies an accessible space that spans at least 25% known eukaryotic motifs. This reveals highly dynamic process capacity broadly explore motifs, allowing rapidly evolve interface. IMPORTANCE Short (SLiMs) are 3–10 amino acid long intrinsically disordered regions (IDRs) serve ubiquitous protein-protein modules cells. Through molecular mimicry, viruses hijack these control cellular It is thought small size SLiMs high mutation frequencies IDRs allow rapid adaptation. However, salient characteristic viruses, due replication errors, their obligate existence mutant swarms. Taking advantage genomic database SARS-CoV-2, here, analyze SLiMs, focusing abundant, find produces abundance transiently present allows efficiently host-virus

Language: Английский

Citations

8
How different viruses perturb host cellular machinery via short linear motifs. DOI

Sobia Idrees,

Keshav Raj Paudel,

Tayyaba Sadaf

et al.

PubMed, Journal Year: 2023, Volume and Issue: 22, P. 1113 - 1128

Published: Jan. 1, 2023

The virus interacts with its hosts by developing protein-protein interactions. Most viruses employ protein interactions to imitate the host protein: A viral same amino acid sequence or structure as attaches protein's binding partner and interferes pathways. Being opportunistic, have evolved manipulate cellular mechanisms mimicking short linear motifs. In this review, we shed light on current understanding of mimicry via motifs focus genetically different subtypes providing recent examples evidence how high-throughput methods can be a reliable source study SLiM-mediated mimicry.

Language: Английский

Citations

6
Molecular mimicry of host short linear motif-mediated interactions utilised by viruses for entry DOI Open Access

Saumyadeep Goswami,

Dibyendu Samanta, Kheerthana Duraivelan

et al.

Molecular Biology Reports, Journal Year: 2023, Volume and Issue: 50(5), P. 4665 - 4673

Published: April 4, 2023

Language: Английский

Citations

5