Lipid-protein interactions: Biosynthetic assembly of CD1 with lipids in the endoplasmic reticulum is evolutionarily conserved

Jang June Park, Suk Jo Kang, A. Dharshan De Silva, Aleksandar K. Stanic, Giulia Casorati, David L. Hachey, Peter Cresswell, Sebastian Joyce

Research output: Contribution to journalArticlepeer-review

Abstract

The CD1 family consists of lipid antigen-presenting molecules, which include group I CD1a, CD1b, and CD1c and group II CD1d proteins. Topologically, they resemble the classical peptide antigen-presenting MHC molecules except that the large, exclusively nonpolar and hydrophobic, antigen-binding groove of CD1 has evolved to present cellular and pathogen-derived lipid antigens to specific T lymphocytes. As an approach to understanding the biochemical basis of lipid antigen presentation by CD1 molecules, we have characterized the natural ligands associated with mouse CD1d1 as well as human CD1b and CD1d molecules. We found that both group I and II CD1 molecules assemble with cellular phosphatidylinositol (PI), which contains heterogeneous fatty acyl chains. Further, this assembly occurs within the endoplasmic reticulum. Because the structures of the antigen-binding grooves of CD1a and CD1c closely resemble those of CD1b and CD1d, we conclude that the assembly of CD1 molecules with PI in the endoplasmic reticulum is evolutionarily conserved. These findings suggest that PI plays a chaperone-like role in CD1 assembly, possibly to preserve the integrity of the antigen-binding groove until CD1 binds antigenic lipids in the endocytic pathway.

Original languageEnglish
Pages (from-to)1022-1026
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number4
DOIs
Publication statusPublished - Jan 27 2004

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Lipid-protein interactions: Biosynthetic assembly of CD1 with lipids in the endoplasmic reticulum is evolutionarily conserved'. Together they form a unique fingerprint.

Cite this