2p6b
Crystal Structure of Human Calcineurin in Complex with PVIVIT PeptideCrystal Structure of Human Calcineurin in Complex with PVIVIT Peptide
Structural highlights
FunctionPP2BA_HUMAN Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.[1] [2] 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 PubMedThe protein phosphatase calcineurin recognizes a wide assortment of substrates and controls diverse developmental and physiological pathways in eukaryotic cells. Dephosphorylation of the transcription factor NFAT and certain other calcineurin substrates depends on docking of calcineurin at a PxIxIT consensus site. We describe here the structural basis for recognition of the PxIxIT sequence by calcineurin. We demonstrate that the high-affinity peptide ligand PVIVIT adds as a beta-strand to the edge of a beta-sheet of calcineurin; that short peptide segments containing the PxIxIT consensus sequence suffice for calcineurin-substrate docking; and that sequence variations within the PxIxIT core modulate the K(d) of the interaction within the physiological range 1 microM to 1 mM. Calcineurin can adapt to a wide variety of substrates, because recognition requires only a PxIxIT sequence and because variation within the core PxIxIT sequence can fine-tune the affinity to match the physiological signalling requirements of individual substrates. Structure of calcineurin in complex with PVIVIT peptide: portrait of a low-affinity signalling interaction.,Li H, Zhang L, Rao A, Harrison SC, Hogan PG J Mol Biol. 2007 Jun 22;369(5):1296-306. Epub 2007 Apr 19. PMID:17498738[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||