PMID- 18339401 OWN - NLM STAT- MEDLINE DCOM- 20080701 LR - 20231213 IS - 1089-8638 (Electronic) IS - 0022-2836 (Linking) VI - 377 IP - 5 DP - 2008 Apr 11 TI - 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. PG - 1297-303 LID - 10.1016/j.jmb.2008.01.098 [doi] AB - 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. FAU - Hoare, Hilary L AU - Hoare HL AD - The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia. FAU - Sullivan, Lucy C AU - Sullivan LC FAU - Clements, Craig S AU - Clements CS FAU - Ely, Lauren K AU - Ely LK FAU - Beddoe, Travis AU - Beddoe T FAU - Henderson, Kate N AU - Henderson KN FAU - Lin, Jie AU - Lin J FAU - Reid, Hugh H AU - Reid HH FAU - Brooks, Andrew G AU - Brooks AG FAU - Rossjohn, Jamie AU - Rossjohn J LA - eng SI - PDB/3BZE SI - PDB/3BZF PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20080212 PL - Netherlands TA - J Mol Biol JT - Journal of molecular biology JID - 2985088R RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (NK Cell Lectin-Like Receptor Subfamily D) RN - 0 (Receptors, Immunologic) SB - IM MH - HLA Antigens/chemistry/*immunology MH - Histocompatibility Antigens Class I/chemistry/*immunology MH - Humans MH - Immunity, Innate/immunology MH - Killer Cells, Natural/immunology/metabolism MH - NK Cell Lectin-Like Receptor Subfamily D/*immunology MH - Protein Conformation MH - Receptors, Immunologic/*immunology/metabolism MH - HLA-E Antigens RF - 30 EDAT- 2008/03/15 09:00 MHDA- 2008/07/02 09:00 CRDT- 2008/03/15 09:00 PHST- 2007/11/05 00:00 [received] PHST- 2008/01/18 00:00 [revised] PHST- 2008/01/22 00:00 [accepted] PHST- 2008/03/15 09:00 [pubmed] PHST- 2008/07/02 09:00 [medline] PHST- 2008/03/15 09:00 [entrez] AID - S0022-2836(08)00177-0 [pii] AID - 10.1016/j.jmb.2008.01.098 [doi] PST - ppublish SO - J Mol Biol. 2008 Apr 11;377(5):1297-303. doi: 10.1016/j.jmb.2008.01.098. Epub 2008 Feb 12.