ArticleProceedings of the National Academy of Sciences of the United States of America2002
A pH-sensitive histidine residue as control element for ligand release from HLA-DR molecules.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- A structural bioinformatics framework for prioritizing pH-sensitive proteins from 3D structural features.BMC bioinformatics · 2026Article
- Selective Enrichment of Antibacterial Peptides from Chicken Hemoglobin Hydrolysates by Electrodialysis with Ultrafiltration Membranes (EDUF).Molecules (Basel, Switzerland) · 2026Article
- RePol: A high-throughput screen for optimizing membrane protein solubilization and purification using polymers.Protein science : a publication of the Protein Society · 2026Article
- Predicting side chain conformations in folded proteins by AlphaFold: Perspective and challenges.Biophysical journal · 2025Article
- Using AlphaFold2 to Predict the Conformations of Side Chains in Folded Proteins.bioRxiv : the preprint server for biology · 2025Article
- Lactic acid inhibits the interaction between PD-L1 protein and PD-L1 antibody in the PD-1/PD-L1 blockade therapy-resistant tumor.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- ANXA10 sensitizes microsatellite instability-high colorectal cancer to anti-PD-1 immunotherapy via assembly of HLA-DR dimers by regulating CD74.Cell biology and toxicology · 2025Article
- Evolution of pH-sensitive transcription termination inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- pH-dependent Synthesis and Interactions of Fluorescent L-Histidine Capped Copper Nanoclusters with Metal Ions.Journal of fluorescence · 2024Article
- Enhancement of subunit vaccine delivery with zinc-carnosine coordination polymer through the addition of mannan.International journal of pharmaceutics · 2024Article
- Isolation of nucleic acids using liquid-liquid phase separation of pH-sensitive elastin-like polypeptides.Scientific reports · 2024Article
- Evolution of pH-sensitive transcription termination during adaptation to repeated long-term starvation.bioRxiv : the preprint server for biology · 2024Article
- Effect of histidine protonation state on ligand binding at the ATP-binding site of human protein kinase CK2.Scientific reports · 2024Article
- Caprin-1 binding to the critical stress granule protein G3BP1 is influenced by pH.Open biology · 2023Article
- The Medicago SymCEP7 hormone increases nodule number via shoots without compromising lateral root number.Plant physiology · 2023Article
- Impact of Pulsed Electric Fields and pH on Enzyme Inactivation and Bioactivities of Peptic Hydrolysates Produced from Bovine and Porcine Hemoglobin.Foods (Basel, Switzerland) · 2022Article
- Ostrinia furnacalis PBP2 solution NMR structure: Insight into ligand binding and release mechanisms.Protein science : a publication of the Protein Society · 2022Article
- Metal-Organic Coordination Polymer for Delivery of a Subunit Broadly Acting Influenza Vaccine.ACS applied materials & interfaces · 2022Article
- Thermoadaptation in an Ancestral Diterpene Cyclase by Altered Loop Stability.The journal of physical chemistry. B · 2022Article
- A stepwise mutagenesis approach using histidine and acidic amino acid to engineer highly pH-dependent protein switches.3 Biotech · 2022Article
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Authors and funding
5 authors.
Funding
Abstract
Class II MHC molecules undergo conformational changes on shifts of the pH. As a consequence, low-affinity peptides tightly bound at pH 7.0 can be released at pH 5.0. The imidazole group of histidine is the only amino acid side chain affected within this range. At pH 5.0 the group is positively charged, polar, and hydrophilic, whereas at pH 7.4 it is neutral, apolar, and hydrophobic. In this study, we used soluble forms of HLA-DR and substituted conserved histidine residues with tyrosine, an isosteric analogue to the uncharged form of histidine. The goal of this substitution was to identify crucial His residues by an increase in pH stability of the ligand complex. HLA-DM-mediated release experiments revealed that substitution of His-33 in the alpha(1) domain of the HLA-DR molecule almost doubled the half-life of HLA-DR1class II-associated invariant-chain peptide complexes. The divergence in the off-rate of WT and H33Y mutated complex was strictly pH-dependent and correlated with the theoretical titration curve of the imidazole group. For both HLA-DR1 and HLA-DR4 molecules the mutation resulted in a shift of class II-associated invariant-chain peptide release curves by up to 0.5 pH units. His-33alpha1 is present in all HLA-DR and H-2E molecules. It connects the alpha(1) and alpha(2) domains in its noncharged form by hydrophobic interactions with residue Val-136alpha2. It is located in close proximity to the putative interface with HLA-DM and may function as a pH-sensitive "button," which is closed at pH 7.0 but opens below pH 6.0 to allow conformational transitions necessary for ligand exchange.
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