2gaz

From Proteopedia

Revision as of 08:57, 21 November 2007

Mycobacterial lipoglycan presentation by CD1d

Overview

Mycobacterial phosphatidylinositol tetramannosides (PIM4) are agonists for, a distinct population of invariant human (Valpha24) and mouse (Valpha14), NKT cells, when presented by CD1d. We determined the crystal structure at, 2.6-A resolution of mouse CD1d bound to a synthetic dipalmitoyl-PIM2., Natural PIM2, which differs in its fatty acid composition is a, biosynthetic precursor of PIM4, PIM6, lipomannan, and lipoarabinomannan., The PIM2 headgroup (inositol-dimannoside) is the most complex to date, among all the crystallized CD1d ligands and is remarkably ordered in the, CD1d binding groove. A specific hydrogen-bonding network between PIM2 and, CD1d orients the headgroup in the center of the binding groove and above, the A' pocket. A central cluster of hydrophilic CD1d residues (Asp(153), Thr(156), Ser(76), Arg(79)) interacts with the phosphate, inositol, and, alpha1-alpha6-linked mannose of the headgroup, whereas additional, specificity for the alpha1- and alpha2-linked mannose is conferred by, Thr(159). The additional two mannoses in PIM4, relative to PIM2, are, located at the distal 6' carbon of the alpha1-alpha6-linked mannose and, would project away from the CD1d binding groove for interaction with the, TCR. Compared with other CD1d-sphingolipid structures, PIM2 has an, increased number of polar interactions between its headgroup and CD1, but, reduced specificity for the diacylglycerol backbone. Thus, novel NKT cell, agonists can be designed that focus on substitutions of the headgroup, rather than on reducing lipid chain length, as in OCH and PBS-25, two, potent variants of the highly stimulatory invariant NKT cell agonist, alpha-galactosylceramide.

About this Structure

2GAZ is a Protein complex structure of sequences from Mus musculus with NAG and XPX as ligands. Full crystallographic information is available from OCA.

Reference

Structural characterization of mycobacterial phosphatidylinositol mannoside binding to mouse CD1d., Zajonc DM, Ainge GD, Painter GF, Severn WB, Wilson IA, J Immunol. 2006 Oct 1;177(7):4577-83. PMID:16982895

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