Compression of functional space in HLA-A sequence diversity.
The major histocompatibility complex (MHC) is highly polymorphic and more than 1500 human MHC alleles are known to date. These alleles do not bind to a given peptide with identical affinity. Although MHC alleles are functionally related, it is difficult to quantify the functional variation between them. Three-dimensional structures of known MHC-peptide (MHCp) complexes suggest that specific peptide residues bind selectively to functional pockets in the binding groove. From a set of known MHCp structures we identified 21 critical polymorphic functional residue positions (CPFRP) that significantly reduced functional pocket variability to just 189 among 212 HLA-A alleles. Interestingly 101 HLA-A alleles clustered into 29 clusters such that the six functional pockets formed by the CPFRPs are identical within the cluster.
Zhao
Bing
B
School of MPE & NCSV, Nanyang Technological University, Singapore.
Png
Adrian Eak H
AE
Ren
Ee Chee
EC
Kolatkar
Prasanna R
PR
Mathura
Venkatarajan Subramaniam
VS
Sakharkar
Meena Kishore
MK
Kangueane
Pandjassarame
P
D000483:Alleles; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015234:HLA-A Antigens / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding
D000596:Amino Acids; D015234:HLA-A Antigens; D010455:Peptides