Venus flytrap or pas de trois? The dynamics of MHC class I molecules

Abstract

The peptide binding site of major histocompatibility complex (MHC) class I molecules is natively unfolded when devoid of peptides. Peptide binding stabilizes the structure and slows the dynamics, but peptide-specific and subtype-specific motions influence, and are influenced by, interaction with assembly chaperones, the T cell receptor, and other class I-binding proteins. The molecular mechanisms of cooperation between peptide, class I heavy chain, and beta-2 microglobulin are insufficiently known but are being elucidated by nuclear magnetic resonance and other modern methods. It appears that micropolymorphic clusters of charged amino acids, often hidden in the molecule interior, determine the dynamics and thus chaperone dependence, cellular fate, and disease association of class I.