Invariant Chain Transmembrane Domain Trimerization: A Step in MHC Class II Assembly

Citations Over TimeTop 16% of 2006 papers

Abstract

The transmembrane (TM) domain of the major histocompatibility complex (MHC) class II-associated invariant chain (Ii) has long been implicated in both correct folding and function of the MHC class II complex. To function correctly, Ii must form a trimer, and the TM domain is one of the domains thought to stabilize the trimeric state. Specific mutations in the TM domain have been shown previously to disrupt MHC class II functions such as mature complex formation and antigen presentation, possibly due to disruption of Ii TM helix-helix interactions. Although this hypothesis has been reported several times in the literature, thus far no experimental measurements have been made to explore the relationship between TM domain structure and TM mutations that affect Ii function. We have applied biophysical and computational methods to study the folding and assembly of the Ii TM domain in isolation and find that the TM domain strongly self-associates. According to analytical ultracentrifugation analyses, the primary oligomeric state for this TM domain is a strongly associated trimer with a dissociation constant of approximately 120 nM in DPC micelles. We have also examined the effect of functionally important mutations of glutamine and threonine residues in the TM domain on its structure, providing results that now link the disruption of TM helix interactions to previously reported losses of Ii function.

Related Papers

• → MHC class II invariant chain homologues in rainbow trout (Oncorhynchus mykiss)(2003)37 cited
• → Substrate determinants of signal peptide peptidase-like 2a (SPPL2a)-mediated intramembrane proteolysis of the invariant chain CD74(2016)27 cited
• The MHC class II-associated invariant chain: a molecule with multiple roles in MHC class II biosynthesis and antigen presentation to CD4+ T cells.(1996)
• → Faculty Opinions recommendation of Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain.(2009)
• → Faculty Opinions recommendation of Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain.(2009)