4Z7I

Crystal structure of insulin regulated aminopeptidase in complex with ligand

Summary for 4Z7I

• Entry DOI: 10.2210/pdb4z7i/pdb
• Descriptor: Leucyl-cystinyl aminopeptidase, DG025 transition-state analogue enzyme inhibitor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: aminopeptidase, antigen presentation, transition-state analogue, enzyme inhibitor, hydrolase, irap
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane ; Single-pass type II membrane protein . Leucyl-cystinyl aminopeptidase, pregnancy serum form: Secreted: Q9UIQ6
• Total number of polymer chains: 4
• Total formula weight: 217286.15

Authors

Mpakali, A.,Saridakis, E.,Harlos, K.,Zhao, Y.,Stratikos, E. (deposition date: 2015-04-07, release date: 2015-08-26, Last modification date: 2024-01-10)

Primary citation

Mpakali, A.,Saridakis, E.,Harlos, K.,Zhao, Y.,Papakyriakou, A.,Kokkala, P.,Georgiadis, D.,Stratikos, E.
Crystal Structure of Insulin-Regulated Aminopeptidase with Bound Substrate Analogue Provides Insight on Antigenic Epitope Precursor Recognition and Processing.
J Immunol., 195:2842-2851, 2015

PubMed Abstract: Aminopeptidases that generate antigenic peptides influence immunodominance and adaptive cytotoxic immune responses. The mechanisms that allow these enzymes to efficiently process a vast number of different long peptide substrates are poorly understood. In this work, we report the structure of insulin-regulated aminopeptidase, an enzyme that prepares antigenic epitopes for cross-presentation in dendritic cells, in complex with an antigenic peptide precursor analog. Insulin-regulated aminopeptidase is found in a semiclosed conformation with an extended internal cavity with limited access to the solvent. The N-terminal moiety of the peptide is located at the active site, positioned optimally for catalysis, whereas the C-terminal moiety of the peptide is stabilized along the extended internal cavity lodged between domains II and IV. Hydrophobic interactions and shape complementarity enhance peptide affinity beyond the catalytic site and support a limited selectivity model for antigenic peptide selection that may underlie the generation of complex immunopeptidomes.

PubMed: 26259583
DOI: 10.4049/jimmunol.1501103

Experimental method

X-RAY DIFFRACTION (3.31 Å)