ArticleNature communications2021
Conformational dynamics linked to domain closure and substrate binding explain the ERAP1 allosteric regulation mechanism.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Chromosome scale genomes of two invasive Adelges species enable virtual screening for selective adelgicides.G3 (Bethesda, Md.) · 2026Article
- Guidelines for the Design of Custom Affinity-Based Probes for Metalloproteases.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Methods and Guidelines for Analyzing the Conformational Dynamics of Proteins in the Antigen Presentation Pathway.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Chromosome scale genomes of two invasive Adelges species enable virtual screening for selective adelgicides.bioRxiv : the preprint server for biology · 2025Article
- Discovery of Novel Allosteric Inhibitor Hits for Insulin-Regulated Aminopeptidase Provides Insights on Enzymatic Mechanism.ACS omega · 2025Article
- Site- and structure-specific characterization of glycoproteins of H11: potent vaccine candidates against parasitic wormFrontiers in immunology · 2025Article
- Stabilization of the open conformation οf insulin-regulated aminopeptidase by a novel substrate-selective small-molecule inhibitor.Protein science : a publication of the Protein Society · 2024Article
- ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights.Journal of medicinal chemistry · 2024Review
- A novel aminopeptidase N/CD13 inhibitor selectively targets an endothelial form of CD13 after coupling to proteins.Cellular and molecular life sciences : CMLS · 2024Article
- Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities.Immunology · 2024Article
- Polymorphic positions 349 and 725 of the autoimmunity-protective allotype 10 of ER aminopeptidase 1 are key in determining its unique enzymatic properties.Frontiers in immunology · 2024Article
- Unraveling the mechanism of ceftaroline-induced allosteric regulation in penicillin-binding protein 2a: insights for novel antibiotic development against methicillin-resistantAntimicrobial agents and chemotherapy · 2023Article
- Review
- Article
- Phosphinic Peptides as Tool Compounds for the Study of Pharmacologically Relevant Zn-Metalloproteases.ACS pharmacology & translational science · 2022Review
- Phenylsulfamoyl Benzoic Acid Inhibitor of ERAP2 with a Novel Mode of Inhibition.ACS chemical biology · 2022Article
- Conformational remodeling enhances activity of lanthipeptide zinc-metallopeptidases.Nature chemical biology · 2022Article
- Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions.Molecules (Basel, Switzerland) · 2022Article
- Can ERAP1 and ERAP2 Form Functional Heterodimers? A Structural Dynamics Investigation.Frontiers in immunology · 2022Article
- Mechanistic diversity in MHC class I antigen recognition.The Biochemical journal · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The endoplasmic-reticulum aminopeptidase ERAP1 processes antigenic peptides for loading on MHC-I proteins and recognition by CD8 T cells as they survey the body for infection and malignancy. Crystal structures have revealed ERAP1 in either open or closed conformations, but whether these occur in solution and are involved in catalysis is not clear. Here, we assess ERAP1 conformational states in solution in the presence of substrates, allosteric activators, and inhibitors by small-angle X-ray scattering. We also characterize changes in protein conformation by X-ray crystallography, and we localize alternate C-terminal binding sites by chemical crosslinking. Structural and enzymatic data suggest that the structural reconfigurations of ERAP1 active site are physically linked to domain closure and are promoted by binding of long peptide substrates. These results clarify steps required for ERAP1 catalysis, demonstrate the importance of conformational dynamics within the catalytic cycle, and provide a mechanism for the observed allosteric regulation and Lys/Arg528 polymorphism disease association.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.