4HS3

Crystal structure of H-2Kb with a disulfide stabilized F pocket in complex with the LCMV derived peptide GP34

Summary for 4HS3

• Entry DOI: 10.2210/pdb4hs3/pdb
• Descriptor: H-2 class I histocompatibility antigen, K-B alpha chain, Beta-2-microglobulin, Envelope glycoprotein, ... (6 entities in total)
• Functional Keywords: mhc class i, antigen presentation, antigen processing, peptide binding, igg, mhc, immune system
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01901; Secreted: P01887
• Total number of polymer chains: 3
• Total formula weight: 44680.14

Authors

Uchtenhagen, H.,Boulanger, B.,Hein, Z.,Abualrous, E.T.,Zacharias, M.,Werner, J.,Elliott, T.,Springer, S.,Achour, A. (deposition date: 2012-10-29, release date: 2014-05-07, Last modification date: 2024-10-09)

Primary citation

Hein, Z.,Uchtenhagen, H.,Abualrous, E.T.,Saini, S.K.,Janen, L.,Van Hateren, A.,Wiek, C.,Hanenberg, H.,Momburg, F.,Achour, A.,Elliott, T.,Springer, S.,Boulanger, D.
Peptide-independent stabilization of MHC class I molecules breaches cellular quality control.
J.Cell.Sci., 127:2885-2897, 2014

PubMed Abstract: The intracellular trafficking of major histocompatibility complex class I (MHC-I) proteins is directed by three quality control mechanisms that test for their structural integrity, which is correlated to the binding of high-affinity antigenic peptide ligands. To investigate which molecular features of MHC-I these quality control mechanisms detect, we have followed the hypothesis that suboptimally loaded MHC-I molecules are characterized by their conformational mobility in the F-pocket region of the peptide-binding site. We have created a novel variant of an MHC-I protein, K(b)-Y84C, in which two α-helices in this region are linked by a disulfide bond that mimics the conformational and dynamic effects of bound high-affinity peptide. K(b)-Y84C shows a remarkable increase in the binding affinity to its light chain, beta-2 microglobulin (β2m), and bypasses all three cellular quality control steps. Our data demonstrate (1) that coupling between peptide and β2m binding to the MHC-I heavy chain is mediated by conformational dynamics; (2) that the folded conformation of MHC-I, supported by β2m, plays a decisive role in passing the ER-to-cell-surface transport quality controls; and (3) that β2m association is also tested by the cell surface quality control that leads to MHC-I endocytosis.

PubMed: 24806963
DOI: 10.1242/jcs.145334

Experimental method

X-RAY DIFFRACTION (2.1 Å)