1a25: Difference between revisions

Revision as of 12:39, 21 February 2008

C2 DOMAIN FROM PROTEIN KINASE C (BETA)

OverviewOverview

BACKGROUND: Conventional isoforms (alpha, beta and gamma) of protein kinase C (PKC) are synergistically activated by phosphatidylserine and Ca2+; both bind to C2 domains located within the PKC amino-terminal regulatory regions. C2 domains contain a bipartite or tripartite Ca2+-binding site formed by opposing loops at one end of the protein. Neither the structural basis for cooperativity between phosphatidylserine and Ca2+, nor the binding site for phosphatidylserine are known. RESULTS: The structure of the C2 domain from PKCbeta complexed with Ca2+ and o-phospho-L-serine has been determined to 2.7 A resolution using X-ray crystallography. The eight-stranded, Greek key beta-sandwich fold of PKCbeta-C2 is similar to that of the synaptotagmin I type I C2 domain. Three Ca2+ ions, one at a novel site, were located, each sharing common aspartate ligands. One of these ligands is donated by a dyad-related C2 molecule. A phosphoserine molecule binds to a lysine-rich cluster in C2. CONCLUSIONS: Shared ligation among the three Ca2+ ions suggests that they bind cooperatively to PKCbeta-C2. Cooperativity may be compromised by the accumulation of positive charge in the binding site as successive ions are bound. Model building shows that the C1 domain could provide carboxylate and carbonyl ligands for two of the three Ca2+ sites. Ca2+-mediated interactions between the two domains could contribute to enzyme activation as well as to the creation of a positively charged phosphatidylserine-binding site.

About this StructureAbout this Structure

1A25 is a Single protein structure of sequence from Rattus norvegicus with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Structure of the protein kinase Cbeta phospholipid-binding C2 domain complexed with Ca2+., Sutton RB, Sprang SR, Structure. 1998 Nov 15;6(11):1395-405. PMID:9817842

Page seeded by OCA on Thu Feb 21 11:39:58 2008

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OCA

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 ==Overview==
-BACKGROUND: Conventional isoforms (alpha, beta and gamma) of protein, kinase C (PKC) are synergistically activated by phosphatidylserine and, Ca2+; both bind to C2 domains located within the PKC amino-terminal, regulatory regions. C2 domains contain a bipartite or tripartite, Ca2+-binding site formed by opposing loops at one end of the protein., Neither the structural basis for cooperativity between phosphatidylserine, and Ca2+, nor the binding site for phosphatidylserine are known. RESULTS:, The structure of the C2 domain from PKCbeta complexed with Ca2+ and, o-phospho-L-serine has been determined to 2.7 A resolution using X-ray, crystallography. The eight-stranded, Greek key beta-sandwich fold of, PKCbeta-C2 is similar to that of the synaptotagmin I type I C2 domain., Three Ca2+ ions, one at a novel site, were located, each sharing common, aspartate ligands. One of these ligands is donated by a dyad-related C2, molecule. A phosphoserine molecule binds to a lysine-rich cluster in C2., CONCLUSIONS: Shared ligation among the three Ca2+ ions suggests that they, bind cooperatively to PKCbeta-C2. Cooperativity may be compromised by the, accumulation of positive charge in the binding site as successive ions are, bound. Model building shows that the C1 domain could provide carboxylate, and carbonyl ligands for two of the three Ca2+ sites. Ca2+-mediated, interactions between the two domains could contribute to enzyme activation, as well as to the creation of a positively charged, phosphatidylserine-binding site.
+BACKGROUND: Conventional isoforms (alpha, beta and gamma) of protein kinase C (PKC) are synergistically activated by phosphatidylserine and Ca2+; both bind to C2 domains located within the PKC amino-terminal regulatory regions. C2 domains contain a bipartite or tripartite Ca2+-binding site formed by opposing loops at one end of the protein. Neither the structural basis for cooperativity between phosphatidylserine and Ca2+, nor the binding site for phosphatidylserine are known. RESULTS: The structure of the C2 domain from PKCbeta complexed with Ca2+ and o-phospho-L-serine has been determined to 2.7 A resolution using X-ray crystallography. The eight-stranded, Greek key beta-sandwich fold of PKCbeta-C2 is similar to that of the synaptotagmin I type I C2 domain. Three Ca2+ ions, one at a novel site, were located, each sharing common aspartate ligands. One of these ligands is donated by a dyad-related C2 molecule. A phosphoserine molecule binds to a lysine-rich cluster in C2. CONCLUSIONS: Shared ligation among the three Ca2+ ions suggests that they bind cooperatively to PKCbeta-C2. Cooperativity may be compromised by the accumulation of positive charge in the binding site as successive ions are bound. Model building shows that the C1 domain could provide carboxylate and carbonyl ligands for two of the three Ca2+ sites. Ca2+-mediated interactions between the two domains could contribute to enzyme activation as well as to the creation of a positively charged phosphatidylserine-binding site.
 ==About this Structure==
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 [[Category: Rattus norvegicus]]
 [[Category: Single protein]]
-[[Category: Sprang, S.R.]]
+[[Category: Sprang, S R.]]
-[[Category: Sutton, R.B.]]
+[[Category: Sutton, R B.]]
 [[Category: CA]]
 [[Category: PSE]]
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 [[Category: calcium-binding protein]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:28:39 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:39:58 2008''