2bc4
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Crystal structure of HLA-DM
OverviewOverview
HLA-DM (DM) plays a critical role in Ag presentation to CD4 T cells by, catalyzing the exchange of peptides bound to MHC class II molecules. Large, lateral surfaces involved in the DM:HLA-DR (DR) interaction have been, defined, but the mechanism of catalysis is not understood. In this study, we describe four small molecules that accelerate DM-catalyzed peptide, exchange. Mechanistic studies demonstrate that these small molecules, substantially enhance the catalytic efficiency of DM, indicating that they, make the transition state of the DM:DR/peptide complex energetically more, favorable. These compounds fall into two functional classes: two compounds, are active only in the presence of DM, and binding data for one show a, direct interaction with DM. The remaining two compounds have partial, activity in the absence of DM, suggesting that they may act at the, interface between DM and DR/peptide. A hydrophobic ridge in the DMbeta1, domain was implicated in the catalysis of peptide exchange because the, activity of three of these enhancers was substantially reduced by point, mutations in this area.
About this StructureAbout this Structure
2BC4 is a Protein complex structure of sequences from Homo sapiens with CL as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Small molecules that enhance the catalytic efficiency of HLA-DM., Nicholson MJ, Moradi B, Seth NP, Xing X, Cuny GD, Stein RL, Wucherpfennig KW, J Immunol. 2006 Apr 1;176(7):4208-20. PMID:16547258
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