User:Joseph Lipsick/SRC: Difference between revisions

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<scene name='User:Joseph_Lipsick/SRC/Activated_c-src/1'>ACTIVATED C-SRC</scene> from PDB 1Y57

Notes: The INACTIVE C-SRC structure was solved with an ATP analog [. The ACTIVE C-SRC structure was solved with an inhibitor that alters the conformation of the kinase activation loop even in the absence of phosphorylation of TYR416 [Cowan-Jacob SW, et al. Structure 13: 861-71 (2005)]. These INACTIVE and ACTIVATED C-SRC structures are shown in similar orientations relative to the kinase (SH1) domain to facilitate an understanding of the mechanism of activation. However, an additional amino-terminal domain (SH4) not shown in either structure tethers the protein to the inner plasma membrane via hydrophobic fatty acid chains (myristate and palmitate) that are covalently bound near the amino terminus of C-SRC. This membrane tethering likely provides a fixed attachment point which the remainder of the protein rolls up towards or opens away from during activation. The SH2 domain of C-SRC can bind to phospho-TYR on other proteins (e.g. an activated receptor tyrosine kinase like PDGF-R), thereby opening the C-SRC protein conformation, exposing phospho-TYR527 to protein phosphatases, and resulting in activation of C-SRC.

Notes: The INACTIVE C-SRC structure was solved with an ATP analog [Xu W, et al. Molec Cell 3: 629-38 (1999)]. The ACTIVE C-SRC structure was solved with an inhibitor that alters the conformation of the kinase activation loop even in the absence of phosphorylation of TYR416 [Cowan-Jacob SW, et al. Structure 13: 861-71 (2005)]. These INACTIVE and ACTIVATED C-SRC structures are shown in similar orientations relative to the kinase (SH1) domain to facilitate an understanding of the mechanism of activation. However, an additional amino-terminal domain (SH4) not shown in either structure tethers the protein to the inner plasma membrane via hydrophobic fatty acid chains (myristate and palmitate) that are covalently bound near the amino terminus of C-SRC. This membrane tethering likely provides a fixed attachment point which the remainder of the protein rolls up towards or opens away from during activation. The SH2 domain of C-SRC can bind to phospho-TYR on other proteins (e.g. an activated receptor tyrosine kinase like PDGF-R), thereby opening the C-SRC protein conformation, exposing phospho-TYR527 to protein phosphatases, and resulting in activation of C-SRC.

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User:Joseph Lipsick/SRC: Difference between revisions

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@@ Line 7: / Line 7: @@
 <scene name='User:Joseph_Lipsick/SRC/Activated_c-src/1'>ACTIVATED C-SRC</scene> from PDB 1Y57
-Notes:  The INACTIVE C-SRC structure was solved with an ATP analog [.  The ACTIVE C-SRC structure was solved with an inhibitor that alters the conformation of the kinase activation loop even in the absence of phosphorylation of TYR416 [Cowan-Jacob SW, et al. Structure 13: 861-71 (2005)].  These INACTIVE and ACTIVATED C-SRC structures are shown in similar orientations relative to the kinase (SH1) domain to facilitate an understanding of the mechanism of activation.  However, an additional amino-terminal domain (SH4) not shown in either structure tethers the protein to the inner plasma membrane via hydrophobic fatty acid chains (myristate and palmitate) that are covalently bound near the amino terminus of C-SRC.  This membrane tethering likely provides a fixed attachment point which the remainder of the protein rolls up towards or opens away from during activation.  The SH2 domain of C-SRC can bind to phospho-TYR on other proteins (e.g. an activated receptor tyrosine kinase like PDGF-R), thereby opening the C-SRC protein conformation, exposing phospho-TYR527 to protein phosphatases, and resulting in activation of C-SRC.
+Notes:  The INACTIVE C-SRC structure was solved with an ATP analog [Xu W, et al. Molec Cell 3: 629-38 (1999)].  The ACTIVE C-SRC structure was solved with an inhibitor that alters the conformation of the kinase activation loop even in the absence of phosphorylation of TYR416 [Cowan-Jacob SW, et al. Structure 13: 861-71 (2005)].  These INACTIVE and ACTIVATED C-SRC structures are shown in similar orientations relative to the kinase (SH1) domain to facilitate an understanding of the mechanism of activation.  However, an additional amino-terminal domain (SH4) not shown in either structure tethers the protein to the inner plasma membrane via hydrophobic fatty acid chains (myristate and palmitate) that are covalently bound near the amino terminus of C-SRC.  This membrane tethering likely provides a fixed attachment point which the remainder of the protein rolls up towards or opens away from during activation.  The SH2 domain of C-SRC can bind to phospho-TYR on other proteins (e.g. an activated receptor tyrosine kinase like PDGF-R), thereby opening the C-SRC protein conformation, exposing phospho-TYR527 to protein phosphatases, and resulting in activation of C-SRC.
 Review Articles: