2p6b
From Proteopedia
(New page: 200px<br /> <applet load="2p6b" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p6b, resolution 2.300Å" /> '''Crystal Structure ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2p6b. | + | [[Image:2p6b.jpg|left|200px]]<br /><applet load="2p6b" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2p6b" size=" | + | |
caption="2p6b, resolution 2.300Å" /> | caption="2p6b, resolution 2.300Å" /> | ||
'''Crystal Structure of Human Calcineurin in Complex with PVIVIT Peptide'''<br /> | '''Crystal Structure of Human Calcineurin in Complex with PVIVIT Peptide'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==Overview== | ||
The 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 muM 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. | The 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 muM 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Cornea plana congenita, recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603288 603288]], Myotonic dystrophy, type 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116955 116955]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2P6B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, FE, PO4 and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2P6B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=FE:'>FE</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P6B OCA]. |
==Reference== | ==Reference== | ||
| Line 28: | Line 24: | ||
[[Category: beta-sheet augmentation; protein-peptide complex]] | [[Category: beta-sheet augmentation; protein-peptide complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:04:41 2008'' |
Revision as of 10:04, 23 January 2008
|
Crystal Structure of Human Calcineurin in Complex with PVIVIT Peptide
Overview
The 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 muM 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.
About this Structure
2P6B is a Protein complex structure of sequences from Homo sapiens with , , and as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Wed Jan 23 12:04:41 2008
