3BZE: The Human Non-Classical Major Histocompatibility Complex Molecule Hla- E

Citation:
Abstract
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.
PDB ID: 3BZEDownload
MMDB ID: 64185
PDB Deposition Date: 2008/1/17
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3BZE: trimeric; determined by author and by software (PISA)
Molecular Components in 3BZE
Label Count Molecule
Proteins (3 molecules)
1
HLA Class I Histocompatibility Antigen, Alpha Chain E(Gene symbol: HLA-E)
Molecule annotation
1
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
1
Leader Peptide of HLA Class I Histocompatibility Alpha Chain G(Gene symbol: HLA-G)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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