Zooming in on the hydrophobic ridge of H-2D(b): implications for the conformational variability of bound peptides.
Class I major histocompatibility complex (MHC) molecules, which display intracellularly processed peptides on the cell surface for scanning by T-cell receptors (TCRs), are extraordinarily polymorphic. MHC polymorphism is believed to result from natural selection, since individuals heterozygous at the corresponding loci can cope with a larger number of pathogens. Here, we present the crystal structures of the murine MHC molecule H-2D(b) in complex with the peptides gp276 and np396 from the lymphocytic choriomeningitis virus (LCMV), solved at 2.18 A and 2.20 A resolution, respectively. The most prominent feature of H-2D(b) is a hydrophobic ridge that cuts across its antigen-binding site, which is conserved in the L(d)-like family of class I MHC molecules. The comparison with previously solved crystal structures of peptide/H-2D(b) complexes shows that the hydrophobic ridge focuses the conformational variability of the bound peptides in a "hot-spot", which could allow optimal TCR interaction and discrimination. This finding suggests a functional reason for the conservation of this structural element.
Ciatto
C
C
Biochemisches Insitut, der Universität Zürich, Winterthurerstrasse 190, Zürich, CH-8057, Switzerland.
Tissot
A C
AC
Tschopp
M
M
Capitani
G
G
Pecorari
F
F
Plückthun
A
A
Grütter
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D019143:Evolution, Molecular; D006183:H-2 Antigens / Q000737:chemistry* / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D006860:Hydrogen Bonding; D008217:Lymphocytic choriomeningitis virus / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010455:Peptides; D011948:Receptors, Antigen, T-Cell