3bzf

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Template:STRUCTURE 3bzf

The human non-classical major histocompatibility complex molecule HLA-E

Overview

Human leukocyte antigen (HLA)-E is a non-classical major histocompatibility complex class I molecule that binds peptides derived from the leader sequences of other HLA class I molecules. Natural killer cell recognition of these HLA-E molecules, via the CD94-NKG2 natural killer family, represents a central innate mechanism for monitoring major histocompatibility complex expression levels within a cell. The leader sequence-derived peptides bound to HLA-E exhibit very limited polymorphism, yet subtle differences affect the recognition of HLA-E by the CD94-NKG2 receptors. To better understand the basis for this peptide-specific recognition, we determined the structure of HLA-E in complex with two leader peptides, namely, HLA-Cw*07 (VMAPRALLL), which is poorly recognised by CD94-NKG2 receptors, and HLA-G*01 (VMAPRTLFL), a high-affinity ligand of CD94-NKG2 receptors. A comparison of these structures, both of which were determined to 2.5-A resolution, revealed that allotypic variations in the bound leader sequences do not result in conformational changes in the HLA-E heavy chain, although subtle changes in the conformation of the peptide within the binding groove of HLA-E were evident. Accordingly, our data indicate that the CD94-NKG2 receptors interact with HLA-E in a manner that maximises the ability of the receptors to discriminate between subtle changes in both the sequence and conformation of peptides bound to HLA-E.

About this Structure

3BZF is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Subtle changes in peptide conformation profoundly affect recognition of the non-classical MHC class I molecule HLA-E by the CD94-NKG2 natural killer cell receptors., Hoare HL, Sullivan LC, Clements CS, Ely LK, Beddoe T, Henderson KN, Lin J, Reid HH, Brooks AG, Rossjohn J, J Mol Biol. 2008 Apr 11;377(5):1297-303. Epub 2008 Feb 12. PMID:18339401 Page seeded by OCA on Wed Apr 30 13:34:21 2008