A conformational change in the human major histocompatibility complex protein HLA-DR1 induced by peptide binding.

Abstract:

:To investigate a conformational change accompanying peptide binding to class II MHC proteins, we probed the structure of a soluble version of the human class II MHC protein HLA-DR1 in empty and peptide-loaded forms. Peptide binding induced a large decrease in the effective radius of the protein as determined by gel filtration, dynamic light scattering, and analytical ultracentrifugation. It caused a substantial increase in the cooperativity of thermal denaturation and induced alterations in MHC polypeptide backbone structure as determined by circular dichroism. These changes suggest a condensation of the protein around the bound peptide. An antibody specific for beta58-69 preferentially bound the empty protein, indicating that the peptide-induced conformational change involves the beta-subunit helical region. The conformational change may have important implications for the mechanisms of intracellular antigen presentation pathways.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Zarutskie JA,Sato AK,Rushe MM,Chan IC,Lomakin A,Benedek GB,Stern LJ

doi

10.1021/bi983048m

subject

Has Abstract

pub_date

1999-05-04 00:00:00

pages

5878-87

issue

18

eissn

0006-2960

issn

1520-4995

pii

bi983048m

journal_volume

38

pub_type

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