2ptk: Difference between revisions
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==Overview== | ==Overview== | ||
The Src protein tyrosine kinase plays a critical role in a variety of, signal transduction pathways. Strict regulation of its activity is, necessary for proper signalling. We present here the crystal structure of, chicken Src which is phosphorylated at Tyr527 and represents its least, active form. Our structure, similar to the recently reported human Hck and, Src structures, contains the SH3, SH2 and the kinase domains and the, C-terminal regulatory tail but not the N-terminal unique domain. The SH3, domain uses its hydrophobic surface to coordinate the SH2-kinase linker, such that residues Gln251 and Leu255 specifically interact with side, chains in the beta2-beta3 and the alphaC-beta4 loops of the N-terminal, lobe opposite of the kinase active site. This position of the SH3 domain, and .. | The Src protein tyrosine kinase plays a critical role in a variety of, signal transduction pathways. Strict regulation of its activity is, necessary for proper signalling. We present here the crystal structure of, chicken Src which is phosphorylated at Tyr527 and represents its least, active form. Our structure, similar to the recently reported human Hck and, Src structures, contains the SH3, SH2 and the kinase domains and the, C-terminal regulatory tail but not the N-terminal unique domain. The SH3, domain uses its hydrophobic surface to coordinate the SH2-kinase linker, such that residues Gln251 and Leu255 specifically interact with side, chains in the beta2-beta3 and the alphaC-beta4 loops of the N-terminal, lobe opposite of the kinase active site. This position of the SH3 domain, and the coordination of the SH2-kinase linker also optimally places the, SH2 domain such that the phosphorylated Tyr527 in the C-terminal tail, interacts with the SH2 binding pocket. Analogous to Cdk2 kinase, the, position of the Src alphaC-helix in the N-terminal lobe is swung out, disrupting the position of the active site residues. Superposition of, other protein kinases including human Hck and Src onto chicken Src, indicate that the alphaC-helix position is affected by the relative, position of the N-terminal lobe with respect to the C-terminal lobe of the, kinase and that the presence of the SH3/SH2-kinase linker/N-terminal lobe, interactions restricts the kinase lobes and alphaC-helix access to the, active conformation. These superpositions also suggest that the highly, conserved alphaC-beta4 loop restricts the conformational freedom of the, N-terminal lobe by anchoring it to the C-terminal lobe. Finally, based on, sequence alignments and conservation of hydrophobic residues in the Src, SH2-kinase linker as well as in the alphaC-beta4 and beta2-beta3 loops, we, propose that the Src-related kinases, Abl, Btk and Csk, share the same, quaternary structure. | ||
==About this Structure== | ==About this Structure== | ||
2PTK is a | 2PTK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.10.1_and_2.7.10.2 Transferred entry: 2.7.10.1 and 2.7.10.2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.112 2.7.1.112] Structure known Active Sites: S1 and S2. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2PTK OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: tyrosine-protein kinase]] | [[Category: tyrosine-protein kinase]] | ||
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Revision as of 14:53, 5 November 2007
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CHICKEN SRC TYROSINE KINASE
OverviewOverview
The Src protein tyrosine kinase plays a critical role in a variety of, signal transduction pathways. Strict regulation of its activity is, necessary for proper signalling. We present here the crystal structure of, chicken Src which is phosphorylated at Tyr527 and represents its least, active form. Our structure, similar to the recently reported human Hck and, Src structures, contains the SH3, SH2 and the kinase domains and the, C-terminal regulatory tail but not the N-terminal unique domain. The SH3, domain uses its hydrophobic surface to coordinate the SH2-kinase linker, such that residues Gln251 and Leu255 specifically interact with side, chains in the beta2-beta3 and the alphaC-beta4 loops of the N-terminal, lobe opposite of the kinase active site. This position of the SH3 domain, and the coordination of the SH2-kinase linker also optimally places the, SH2 domain such that the phosphorylated Tyr527 in the C-terminal tail, interacts with the SH2 binding pocket. Analogous to Cdk2 kinase, the, position of the Src alphaC-helix in the N-terminal lobe is swung out, disrupting the position of the active site residues. Superposition of, other protein kinases including human Hck and Src onto chicken Src, indicate that the alphaC-helix position is affected by the relative, position of the N-terminal lobe with respect to the C-terminal lobe of the, kinase and that the presence of the SH3/SH2-kinase linker/N-terminal lobe, interactions restricts the kinase lobes and alphaC-helix access to the, active conformation. These superpositions also suggest that the highly, conserved alphaC-beta4 loop restricts the conformational freedom of the, N-terminal lobe by anchoring it to the C-terminal lobe. Finally, based on, sequence alignments and conservation of hydrophobic residues in the Src, SH2-kinase linker as well as in the alphaC-beta4 and beta2-beta3 loops, we, propose that the Src-related kinases, Abl, Btk and Csk, share the same, quaternary structure.
About this StructureAbout this Structure
2PTK is a Single protein structure of sequence from Gallus gallus. Active as Transferred entry: 2.7.10.1 and 2.7.10.2, with EC number 2.7.1.112 Structure known Active Sites: S1 and S2. Full crystallographic information is available from OCA.
ReferenceReference
The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions., Williams JC, Weijland A, Gonfloni S, Thompson A, Courtneidge SA, Superti-Furga G, Wierenga RK, J Mol Biol. 1997 Dec 19;274(5):757-75. PMID:9405157
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