Function-related regulation of the stability of MHC proteins.
Proteins must be stable to accomplish their biological function and to avoid enzymatic degradation. Constitutive proteolysis, however, is the main source of free amino acids used for de novo protein synthesis. In this paper the delicate balance of protein stability and degradability is discussed in the context of function of major histocompatibility complex (MHC) encoded protein. Classical MHC proteins are single-use peptide transporters that carry proteolytic degradation products to the cell surface for presenting them to T cells. These proteins fulfill their function as long as they bind their dissociable ligand, the peptide. Ligand-free MHC molecules on the cell surface are practically useless for their primary biological function, but may acquire novel activity or become an important source of amino acids when they lose their compact stable structure, which resists proteolytic attacks. We show in this paper that one or more of the stabilization centers responsible for the stability of MHC-peptide complexes is composed of residues of both the protein and the peptide, therefore missing in the ligand-free protein. This arrangement of stabilization centers provides a simple means of regulation; it makes the useful form of the protein stable, whereas the useless form of the same protein is unstable and therefore degradable.
Simon
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A
Institute of Enzymology, Hungarian Academy of Sciences, H-1518 Budapest, P.O. Box 7, Hungary.
Dosztányi
Z s
Zs
Rajnavölgyi
E
E
Simon
I
I
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D004355:Drug Stability; D006183:H-2 Antigens / Q000737:chemistry* / Q000378:metabolism*; D006680:HLA Antigens / Q000737:chemistry* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary
D006183:H-2 Antigens; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D009842:Oligopeptides