2jpw
From Proteopedia
(New page: 200px<br /><applet load="2jpw" size="350" color="white" frame="true" align="right" spinBox="true" caption="2jpw" /> '''Solution structure of the bisphosphorylated ...) |
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==Overview== | ==Overview== | ||
| - | We present here the solution structure for the bisphosphorylated form of | + | We present here the solution structure for the bisphosphorylated form of the cardiac N-extension of troponin I (cTnI(1-32)), a region for which there are no previous high-resolution data. Using this structure, the X-ray crystal structure of the cardiac troponin core, and uniform density models of the troponin components derived from neutron contrast variation data, we built atomic models for troponin that show the conformational transition in cardiac troponin induced by bisphosphorylation. In the absence of phosphorylation, our NMR data and sequence analyses indicate a less structured cardiac N-extension with a propensity for a helical region surrounding the phosphorylation motif, followed by a helical C-terminal region (residues 25-30). In this conformation, TnI(1-32) interacts with the N-lobe of cardiac troponin C (cTnC) and thus is positioned to modulate myofilament Ca2+-sensitivity. Bisphosphorylation at Ser23/24 extends the C-terminal helix (residues 21-30) which results in weakening interactions with the N-lobe of cTnC and a re-positioning of the acidic amino terminus of cTnI(1-32) for favorable interactions with basic regions, likely the inhibitory region of cTnI. An extended poly(L-proline)II helix between residues 11 and 19 serves as the rigid linker that aids in re-positioning the amino terminus of cTnI(1-32) upon bisphosphorylation at Ser23/24. We propose that it is these electrostatic interactions between the acidic amino terminus of cTnI(1-32) and the basic inhibitory region of troponin I that induces a bending of cTnI at the end that interacts with cTnC. This model provides a molecular mechanism for the observed changes in cross-bridge kinetics upon TnI phosphorylation. |
==About this Structure== | ==About this Structure== | ||
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Phosphorylation-dependent conformational transition of the cardiac specific N-extension of troponin I in cardiac troponin., Howarth JW, Meller J, Solaro RJ, Trewhella J, Rosevear PR, J Mol Biol. 2007 Oct 26;373(3):706-22. Epub 2007 Aug 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17854829 17854829] | Phosphorylation-dependent conformational transition of the cardiac specific N-extension of troponin I in cardiac troponin., Howarth JW, Meller J, Solaro RJ, Trewhella J, Rosevear PR, J Mol Biol. 2007 Oct 26;373(3):706-22. Epub 2007 Aug 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17854829 17854829] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Howarth, J | + | [[Category: Howarth, J W.]] |
[[Category: Meller, J.]] | [[Category: Meller, J.]] | ||
| - | [[Category: Rosevear, P | + | [[Category: Rosevear, P R.]] |
| - | [[Category: Solaro, R | + | [[Category: Solaro, R J.]] |
[[Category: Trewhella, J.]] | [[Category: Trewhella, J.]] | ||
[[Category: PO3]] | [[Category: PO3]] | ||
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[[Category: poly (l-proline) ii helix]] | [[Category: poly (l-proline) ii helix]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:05:03 2008'' |
Revision as of 16:05, 21 February 2008
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Solution structure of the bisphosphorylated cardiac specific N-extension of cardiac troponin I
Overview
We present here the solution structure for the bisphosphorylated form of the cardiac N-extension of troponin I (cTnI(1-32)), a region for which there are no previous high-resolution data. Using this structure, the X-ray crystal structure of the cardiac troponin core, and uniform density models of the troponin components derived from neutron contrast variation data, we built atomic models for troponin that show the conformational transition in cardiac troponin induced by bisphosphorylation. In the absence of phosphorylation, our NMR data and sequence analyses indicate a less structured cardiac N-extension with a propensity for a helical region surrounding the phosphorylation motif, followed by a helical C-terminal region (residues 25-30). In this conformation, TnI(1-32) interacts with the N-lobe of cardiac troponin C (cTnC) and thus is positioned to modulate myofilament Ca2+-sensitivity. Bisphosphorylation at Ser23/24 extends the C-terminal helix (residues 21-30) which results in weakening interactions with the N-lobe of cTnC and a re-positioning of the acidic amino terminus of cTnI(1-32) for favorable interactions with basic regions, likely the inhibitory region of cTnI. An extended poly(L-proline)II helix between residues 11 and 19 serves as the rigid linker that aids in re-positioning the amino terminus of cTnI(1-32) upon bisphosphorylation at Ser23/24. We propose that it is these electrostatic interactions between the acidic amino terminus of cTnI(1-32) and the basic inhibitory region of troponin I that induces a bending of cTnI at the end that interacts with cTnC. This model provides a molecular mechanism for the observed changes in cross-bridge kinetics upon TnI phosphorylation.
About this Structure
2JPW is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Phosphorylation-dependent conformational transition of the cardiac specific N-extension of troponin I in cardiac troponin., Howarth JW, Meller J, Solaro RJ, Trewhella J, Rosevear PR, J Mol Biol. 2007 Oct 26;373(3):706-22. Epub 2007 Aug 22. PMID:17854829
Page seeded by OCA on Thu Feb 21 18:05:03 2008
