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Publication Abstract from PubMed

Tapasin is a glycoprotein critical for loading major histocompatibility complex (MHC) class I molecules with high-affinity peptides. It functions within the multimeric peptide-loading complex (PLC) as a disulfide-linked, stable heterodimer with the thiol oxidoreductase ERp57, and this covalent interaction is required to support optimal PLC activity. Here, we present the 2.6 A resolution structure of the tapasin-ERp57 core of the PLC. The structure revealed that tapasin interacts with both ERp57 catalytic domains, accounting for the stability of the heterodimer, and provided an example of a protein disulfide isomerase family member interacting with substrate. Mutational analysis identified a conserved surface on tapasin that interacted with MHC class I molecules and was critical for peptide loading and editing functions of the tapasin-ERp57 heterodimer. By combining the tapasin-ERp57 structure with those of other defined PLC components, we present a molecular model that illuminates the processes involved in MHC class I peptide loading.

Insights into MHC Class I Peptide Loading from the Structure of the Tapasin-ERp57 Thiol Oxidoreductase Heterodimer.,Dong G, Wearsch PA, Peaper DR, Cresswell P, Reinisch KM Immunity. 2008 Dec 30. PMID:19119025^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.