3UO1

Structure of a monoclonal antibody complexed with its MHC-I antigen

Summary for 3UO1

• Entry DOI: 10.2210/pdb3uo1/pdb
• Related: 3UYR 3V4U 3V52
• Descriptor: ANTI-MHC-I MONOCLONAL ANTIBODY, 64-3-7 H CHAIN, ANTI-MHC-I MONOCLONAL ANTIBODY, 64-3-7 L CHAIN, H-2 class I histocompatibility antigen, L-D alpha chain, ... (5 entities in total)
• Functional Keywords: ig-fold, 3, 10-helix, immune system
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01897
• Total number of polymer chains: 3
• Total formula weight: 48342.77

Authors

Margulies, D.H.,Mage, M.G.,Wang, R.,Natarajan, K. (deposition date: 2011-11-16, release date: 2012-07-25, Last modification date: 2012-08-01)

Primary citation

Mage, M.G.,Dolan, M.A.,Wang, R.,Boyd, L.F.,Revilleza, M.J.,Robinson, H.,Natarajan, K.,Myers, N.B.,Hansen, T.H.,Margulies, D.H.
The Peptide-receptive transition state of MHC class I molecules: insight from structure and molecular dynamics.
J.Immunol., 189:1391-1399, 2012

PubMed Abstract: MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I-restricted CD8(+) T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 3(10) helix that flips from an exposed "open" position in the PR transition state to a "closed" position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46-53 of murine H-2L(d) MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation.

PubMed: 22753930
DOI: 10.4049/jimmunol.1200831

Experimental method

X-RAY DIFFRACTION (1.641 Å)