2gto
Oxidized form of ADAP hSH3-N
Structural highlights
Function[FYB_HUMAN] Acts as an adapter protein of the FYN and LCP2 signaling cascades in T-cells. Modulates the expression of interleukin-2 (IL-2). Involved in platelet activation. Prevents the degradation of SKAP1 and SKAP2. May play a role in linking T-cell signaling to remodeling of the actin cytoskeleton.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedOxidation-induced conformational changes in proteins provide a powerful mechanism to sense the redox state of a living cell. In contrast to the unspecific and often irreversible oxidation of intracellular proteins during severe oxidative stress, regulatory redox events need to have specific and transient effects on cellular targets. Here we present evidence for the reversible formation of a vicinal disulfide bond in a prototypic protein interaction domain. NMR spectroscopy was used to determine the structure of the N-terminal hSH3 domain (hSH3N) of the immune cell protein ADAP (adhesion and degranulation promoting adapter protein) in the reduced and oxidized states. An eight-membered ring formed upon oxidation of two neighboring cysteines leads to significant changes in the variable arginine-threonine (RT) loop of the hSH3N domain and alters the helix-sheet packing of the domain. The redox potential for this structural transition is -228 mV at pH 7.4. This is compatible with a role of the cysteinylcysteine moiety in redox signaling during T cell activation. Redox-regulated conformational changes in an SH3 domain.,Zimmermann J, Kuhne R, Sylvester M, Freund C Biochemistry. 2007 Jun 12;46(23):6971-7. Epub 2007 May 19. PMID:17511475[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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