1wbp

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==Overview==
==Overview==
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The arginine-serine (RS)-rich domain of the SR protein ASF/SF2 is, phosphorylated by SR protein kinases (SRPKs) and Clk/Sty kinases. However, the mode of phosphorylation by these kinases and their coordination in the, biological regulation of ASF/SF2 is unknown. Here, we report the crystal, structure of an active fragment of human SRPK1 bound to a peptide derived, from an SR protein. This structure led us to identify a docking motif in, ASF/SF2. We find that this docking motif restricts phosphorylation of, ASF/SF2 by SRPK1 to the N-terminal part of the RS domain - a property, essential for its assembly into nuclear speckles. We further show that, Clk/Sty causes release of ASF/SF2 from speckles by phosphorylating the, C-terminal part of its RS domain. These results suggest that the docking, motif of ASF/SF2 is a key regulatory element for sequential, phosphorylation by SRPK1 and Clk/Sty and, thus, is essential for its, subcellular localization.
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The arginine-serine (RS)-rich domain of the SR protein ASF/SF2 is phosphorylated by SR protein kinases (SRPKs) and Clk/Sty kinases. However, the mode of phosphorylation by these kinases and their coordination in the biological regulation of ASF/SF2 is unknown. Here, we report the crystal structure of an active fragment of human SRPK1 bound to a peptide derived from an SR protein. This structure led us to identify a docking motif in ASF/SF2. We find that this docking motif restricts phosphorylation of ASF/SF2 by SRPK1 to the N-terminal part of the RS domain - a property essential for its assembly into nuclear speckles. We further show that Clk/Sty causes release of ASF/SF2 from speckles by phosphorylating the C-terminal part of its RS domain. These results suggest that the docking motif of ASF/SF2 is a key regulatory element for sequential phosphorylation by SRPK1 and Clk/Sty and, thus, is essential for its subcellular localization.
==About this Structure==
==About this Structure==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Transferred entry: 2.7.11.1]]
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[[Category: Transferred entry: 2 7.11 1]]
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[[Category: Adams, J.A.]]
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[[Category: Adams, J A.]]
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[[Category: Aubol, B.E.]]
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[[Category: Aubol, B E.]]
[[Category: Chakrabarti, S.]]
[[Category: Chakrabarti, S.]]
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[[Category: Ding, J.H.]]
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[[Category: Ding, J H.]]
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[[Category: Fu, X.D.]]
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[[Category: Fu, X D.]]
[[Category: Ghosh, G.]]
[[Category: Ghosh, G.]]
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[[Category: Ngo, J.C.]]
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[[Category: Ngo, J C.]]
[[Category: Nolen, B.]]
[[Category: Nolen, B.]]
[[Category: Velazquez-Dones, A.]]
[[Category: Velazquez-Dones, A.]]
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:21:31 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:42:32 2008''

Revision as of 13:42, 21 February 2008


1wbp, resolution 2.40Å

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SRPK1 BOUND TO 9MER DOCKING MOTIF PEPTIDE

Overview

The arginine-serine (RS)-rich domain of the SR protein ASF/SF2 is phosphorylated by SR protein kinases (SRPKs) and Clk/Sty kinases. However, the mode of phosphorylation by these kinases and their coordination in the biological regulation of ASF/SF2 is unknown. Here, we report the crystal structure of an active fragment of human SRPK1 bound to a peptide derived from an SR protein. This structure led us to identify a docking motif in ASF/SF2. We find that this docking motif restricts phosphorylation of ASF/SF2 by SRPK1 to the N-terminal part of the RS domain - a property essential for its assembly into nuclear speckles. We further show that Clk/Sty causes release of ASF/SF2 from speckles by phosphorylating the C-terminal part of its RS domain. These results suggest that the docking motif of ASF/SF2 is a key regulatory element for sequential phosphorylation by SRPK1 and Clk/Sty and, thus, is essential for its subcellular localization.

About this Structure

1WBP is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2., Ngo JC, Chakrabarti S, Ding JH, Velazquez-Dones A, Nolen B, Aubol BE, Adams JA, Fu XD, Ghosh G, Mol Cell. 2005 Oct 7;20(1):77-89. PMID:16209947

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