3BZF

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

Summary for 3BZF

• Entry DOI: 10.2210/pdb3bzf/pdb
• Related: 3BZE
• Descriptor: HLA class I histocompatibility antigen, alpha chain E, Beta-2-microglobulin, leader peptide of HLA class I histocompatibility antigen, Cw-7 alpha chain, ... (4 entities in total)
• Functional Keywords: mhc fold, glycoprotein, immune response, membrane, mhc i, polymorphism, transmembrane, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, host-virus interaction, ubl conjugation, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P13747 P10321; Secreted: P61769
• Total number of polymer chains: 6
• Total formula weight: 88830.60

Authors

Hoare, H.L.,Sullivan, L.C.,Ely, L.K.,Beddoe, T.,Henderson, K.N.,Lin, J.,Clements, C.S.,Reid, H.H.,Brooks, A.G.,Rossjohn, J. (deposition date: 2008-01-17, release date: 2008-04-29, Last modification date: 2024-10-09)

Primary citation

Hoare, H.L.,Sullivan, L.C.,Clements, C.S.,Ely, L.K.,Beddoe, T.,Henderson, K.N.,Lin, J.,Reid, H.H.,Brooks, A.G.,Rossjohn, J.
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
J.Mol.Biol., 377:1297-1303, 2008

PubMed 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.

PubMed: 18339401
DOI: 10.1016/j.jmb.2008.01.098

Experimental method

X-RAY DIFFRACTION (2.5 Å)