Solution structure of human survivin and its binding interface with Smac/Diablo.
NMR studies of the antiapoptotic protein survivin have been used to determine the homodimer interface of the protein in solution and to identify residues of the protein that interact with Smac/Diablo. In solution, survivin(1-120) forms a bow-tie-shaped dimer whose interface is composed of its N-terminal residues as well as residues connecting its BIR domain to the C-terminal alpha helix. The solution structure resolves the controversy regarding the two possible dimer interfaces for survivin observed in X-ray crystal structures. The structural basis for the interaction between survivin and Smac/Diablo was also investigated. When Smac/Diablo or N-terminal Smac/Diablo peptide analogues are added to a solution of survivin, specific residues near alpha4 and beta3 are perturbed. NMR experiments indicate that the peptides bind across the third beta-strand of survivin in a manner similar to the way Smac/Diablo peptides bind to the BIR3 domain of X-linked IAP (XIAP).
Sun
Chaohong
C
Global Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064-6098, USA.
Nettesheim
David
D
Liu
Zhihong
Z
Olejniczak
Edward T
ET
D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009682:Magnetic Resonance Spectroscopy; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009363:Neoplasm Proteins; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012996:Solutions; D000077022:Survivin
D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D002352:Carrier Proteins; C412403:DIABLO protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012996:Solutions; D000077022:Survivin