Endogenous phosphatidylcholine and a long spacer ligand stabilize the lipid-binding groove of CD1b
Open Access
- 27 July 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 25 (15), 3684-3692
- https://doi.org/10.1038/sj.emboj.7601244
Abstract
CD1 proteins present lipid antigens to T cells. The antigens are acquired in the endosomal compartments. This raises the question of how the large hydrophobic CD1 pockets are preserved between the moment of biosynthesis in the endoplasmic reticulum and arrival to the endosomes. To address this issue, the natural ligands associated with a soluble form of human CD1b have been investigated. Using isoelectric focusing, native mass spectrometry and resolving the crystal structure at 1.8 Å resolution, we found that human CD1b is simultaneously associated with endogenous phosphatidylcholine (PC) and a 41–44 carbon atoms‐long spacer molecule. The two lipids appear to work in concert to stabilize the CD1b groove, their combined size slightly exceeding the maximal groove capacity. We propose that the spacer serves to prevent binding of ligands with long lipid tails, whereas short‐chain lipids might still displace the PC, which is exposed at the groove entrance. The data presented herein explain how the CD1b groove is preserved, and provide a rationale for the in vivo antigen‐binding properties of CD1b.Keywords
This publication has 43 references indexed in Scilit:
- Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cellsThe Journal of Experimental Medicine, 2005
- Recognition of lipid antigens by T cellsNature Reviews Immunology, 2005
- Anatomy of CD1–lipid antigen complexesNature Reviews Immunology, 2005
- CD1a and CD1b surface expression is independent from de novo synthesized glycosphingolipidsEuropean Journal of Immunology, 2002
- In This IssueNature Reviews Molecular Cell Biology, 2002
- Structure of human CD1b with bound ligands at 2.3 Å, a maze for alkyl chainsNature Immunology, 2002
- Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentationNature Immunology, 2002
- Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand designProtein Science, 1998
- Refinement of Macromolecular Structures by the Maximum-Likelihood MethodActa Crystallographica Section D-Biological Crystallography, 1997
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Biological Crystallography, 1994