1a9b
DECAMER-LIKE CONFORMATION OF A NANO-PEPTIDE BOUND TO HLA-B3501 DUE TO NONSTANDARD POSITIONING OF THE C-TERMINUS
|
OverviewOverview
The N and C termini of peptides presented by major histocompatibility, complex (MHC) class I molecules are held within the peptide binding groove, by a network of hydrogen bonds to conserved MHC residues. However, the, published structure of the human allele HLA-B*3501 complexed with the nef, octa-peptide VPLRPMTY, revealed non-standard positioning for both peptide, termini. To investigate whether these deviations are indeed related to the, length of the nef-peptide, we have determined the structure of HLA-B*3501, presenting a nona-peptide to 2.5 A resolution. A comparison of, HLA-B*3501/peptide complexes with structures of other HLA molecules, exhibits allele-specific properties of HLA-B*3501, as well as, peptide-induced structural changes. Independent of the length of the bound, peptide, HLA-B*3501 positions the peptide C terminus significantly closer, to the alpha1-helix and nearer to the A pocket than observed for other HLA, class I/peptide complexes. This reorientation is accompanied by a shift, within the N-terminal part of the alpha2-helix towards the middle of the, binding groove. Due to the short distance between the N and C termini, the, nona-peptide is compressed and forced to zig-zag vertically within the, binding groove. Its conformation rather resembles that of a deca-peptide, than of other nona-peptides bound to class I molecules. Superposition of, both HLA-B*3501/peptide complexes additionally reveals a significant, peptide-dependent deviation between the N-terminal parts of the, alpha1-helices which might be due to different positioning of the peptide, N termini. Taken together, these data illustrate the strong, interdependence between the HLA class I molecule and the bound peptide.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]
About this StructureAbout this Structure
1A9B is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Decamer-like conformation of a nona-peptide bound to HLA-B*3501 due to non-standard positioning of the C terminus., Menssen R, Orth P, Ziegler A, Saenger W, J Mol Biol. 1999 Jan 15;285(2):645-53. PMID:9878435
Page seeded by OCA on Mon Nov 12 15:56:57 2007