2oza: Difference between revisions

Revision as of 19:24, 21 February 2008

Structure of p38alpha complex

OverviewOverview

p38 MAPK and MAPK-activated protein kinase 2 (MK2) are key components of signaling pathways leading to many cellular responses, notably the proinflammatory cytokine production. The physical association of p38alpha isoform and MK2 is believed to be physiologically important for this signaling. We report the 2.7-A resolution crystal structure of the unphosphorylated complex between p38alpha and MK2. These protein kinases bind "head-to-head," present their respective active sites on approximately the same side of the heterodimer, and form extensive intermolecular interactions. Among these interactions, the MK2 Ile-366-Ala-390, which includes the bipartite nuclear localization signal, binds to the p38alpha-docking region. This binding supports the involvement of noncatalytic regions to the tight binding of the MK2:p38alpha binary assembly. The MK2 residues 345-365, containing the nuclear export signal, block access to the p38alpha active site. Some regulatory phosphorylation regions of both protein kinases engage in multiple interactions with one another in this complex. This structure gives new insights into the regulation of the protein kinases p38alpha and MK2, aids in the better understanding of their known cellular and biochemical studies, and provides a basis for understanding other regulatory protein-protein interactions involving signal transduction proteins.

About this StructureAbout this Structure

2OZA is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.

ReferenceReference

Molecular basis of MAPK-activated protein kinase 2:p38 assembly., White A, Pargellis CA, Studts JM, Werneburg BG, Farmer BT 2nd, Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6353-8. Epub 2007 Mar 29. PMID:17395714

Page seeded by OCA on Thu Feb 21 18:24:09 2008

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OCA

@@ Line 4: / Line 4: @@
 ==Overview==
-p38 MAPK and MAPK-activated protein kinase 2 (MK2) are key components of, signaling pathways leading to many cellular responses, notably the, proinflammatory cytokine production. The physical association of p38alpha, isoform and MK2 is believed to be physiologically important for this, signaling. We report the 2.7-A resolution crystal structure of the, unphosphorylated complex between p38alpha and MK2. These protein kinases, bind "head-to-head," present their respective active sites on, approximately the same side of the heterodimer, and form extensive, intermolecular interactions. Among these interactions, the MK2, Ile-366-Ala-390, which includes the bipartite nuclear localization signal, binds to the p38alpha-docking region. This binding supports the, involvement of noncatalytic regions to the tight binding of the, MK2:p38alpha binary assembly. The MK2 residues 345-365, containing the, nuclear export signal, block access to the p38alpha active site. Some, regulatory phosphorylation regions of both protein kinases engage in, multiple interactions with one another in this complex. This structure, gives new insights into the regulation of the protein kinases p38alpha and, MK2, aids in the better understanding of their known cellular and, biochemical studies, and provides a basis for understanding other, regulatory protein-protein interactions involving signal transduction, proteins.
+p38 MAPK and MAPK-activated protein kinase 2 (MK2) are key components of signaling pathways leading to many cellular responses, notably the proinflammatory cytokine production. The physical association of p38alpha isoform and MK2 is believed to be physiologically important for this signaling. We report the 2.7-A resolution crystal structure of the unphosphorylated complex between p38alpha and MK2. These protein kinases bind "head-to-head," present their respective active sites on approximately the same side of the heterodimer, and form extensive intermolecular interactions. Among these interactions, the MK2 Ile-366-Ala-390, which includes the bipartite nuclear localization signal, binds to the p38alpha-docking region. This binding supports the involvement of noncatalytic regions to the tight binding of the MK2:p38alpha binary assembly. The MK2 residues 345-365, containing the nuclear export signal, block access to the p38alpha active site. Some regulatory phosphorylation regions of both protein kinases engage in multiple interactions with one another in this complex. This structure gives new insights into the regulation of the protein kinases p38alpha and MK2, aids in the better understanding of their known cellular and biochemical studies, and provides a basis for understanding other regulatory protein-protein interactions involving signal transduction proteins.
 ==About this Structure==
@@ Line 15: / Line 15: @@
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Protein complex]]
-[[Category: II, B.T.Farmer.]]
+[[Category: II, B T.Farmer.]]
-[[Category: Pargellis, C.A.]]
+[[Category: Pargellis, C A.]]
-[[Category: Studts, J.M.]]
+[[Category: Studts, J M.]]
-[[Category: Werneburg, B.G.]]
+[[Category: Werneburg, B G.]]
 [[Category: White, A.]]
 [[Category: mk2]]
@@ Line 25: / Line 25: @@
 [[Category: serine/threonine kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:32:58 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:24:09 2008''