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Structure of an S100A7 triple mutant
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedS100A7 (psoriasin) is a calcium and zinc-binding protein implicated in breast cancer. We have shown previously that S100A7 enhances survival mechanisms in breast cells through an interaction with c-jun activation domain binding protein 1 (Jab1), and an engineered S100A7 triple mutant (Asp(56)Gly, Leu(78)Met, and Gln(88)Lys - S100A7(3)) ablates Jab1 binding. Here we extend these results to include defined breast cancer cell lines and demonstrate a disrupted S100A7(3)/Jab1 phenotype is maintained. To establish the basis for the abrogated Jab1 binding we have recombinantly produced S100A7(3), demonstrated that it retains the ability to form an exceptionally thermostable dimer and solved the three dimensional crystal structure to 1.6 A. Despite being positioned at the dimer interface, the Leu(78)Met mutation is easily accommodated and contributes to a methionine rich pocket formed by Met(12), Met(15), Met(34). In addition to altering the surface charge, the Gln(88)Lys mutation results in a nearby rotameric shift in Tyr(85) leading to a substantially reorganized surface cavity and may influence zinc binding. The final mutation of Asp(56) to Gly results in the largest structural perturbation shortening helix IV by one full turn. It is noteworthy that position 56 lies in one of two divergent clusters between S100A7 and the functionally distinct yet highly homologous S100A15. The structure of S100A7(3) provides a unique perspective from which to characterize the S100A7-Jab1 interaction and better understand the distinct functions between S100A7 and its closely related paralog S100A15. (c) 2009 The Protein Society. Structural and functional characterization of a triple mutant form of S100A7 defective for Jab1 binding.,West NR, Farnell B, Murray JI, Hof F, Watson PH, Boulanger MJ Protein Sci. 2009 Oct 20. PMID:19844956[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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