1w5h: Difference between revisions

Revision as of 16:40, 21 February 2008

AN ANTI-PARALLEL FOUR HELIX BUNDLE.

OverviewOverview

A detailed understanding of the mechanisms by which particular amino acid sequences can give rise to more than one folded structure, such as for proteins that undergo large conformational changes or misfolding, is a long-standing objective of protein chemistry. Here, we describe the crystal structures of a single coiled-coil peptide in distinct parallel and antiparallel tetrameric configurations and further describe the parallel or antiparallel crystal structures of several related peptide sequences; the antiparallel tetrameric assemblies represent the first crystal structures of GCN4-derived peptides exhibiting such a configuration. Intriguingly, substitution of a single solvent-exposed residue enabled the parallel coiled-coil tetramer GCN4-pLI to populate the antiparallel configuration, suggesting that the two configurations are close enough in energy for subtle sequence changes to have important structural consequences. We present a structural analysis of the small changes to the helix register and side-chain conformations that accommodate the two configurations and have supplemented these results using solution studies and a molecular dynamics energetic analysis using a replica exchange methodology. Considering the previous examples of structural nonspecificity in coiled-coil peptides, the findings reported here not only emphasize the predisposition of the coiled-coil motif to adopt multiple configurations but also call attention to the associated risk that observed crytstal structures may not represent the only (or even the major) species present in solution.

About this StructureAbout this Structure

1W5H is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

ReferenceReference

Coiled coils at the edge of configurational heterogeneity. Structural analyses of parallel and antiparallel homotetrameric coiled coils reveal configurational sensitivity to a single solvent-exposed amino acid substitution., Yadav MK, Leman LJ, Price DJ, Brooks CL 3rd, Stout CD, Ghadiri MR, Biochemistry. 2006 Apr 11;45(14):4463-73. PMID:16584182

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OCA

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-[[Image:1w5h.gif|left|200px]]<br /><applet load="1w5h" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1w5h.gif|left|200px]]<br /><applet load="1w5h" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1w5h, resolution 2.50&Aring;" />
 '''AN ANTI-PARALLEL FOUR HELIX BUNDLE.'''<br />
 ==Overview==
-A detailed understanding of the mechanisms by which particular amino acid, sequences can give rise to more than one folded structure, such as for, proteins that undergo large conformational changes or misfolding, is a, long-standing objective of protein chemistry. Here, we describe the, crystal structures of a single coiled-coil peptide in distinct parallel, and antiparallel tetrameric configurations and further describe the, parallel or antiparallel crystal structures of several related peptide, sequences; the antiparallel tetrameric assemblies represent the first, crystal structures of GCN4-derived peptides exhibiting such a, configuration. Intriguingly, substitution of a single solvent-exposed, residue enabled the parallel coiled-coil tetramer GCN4-pLI to populate the, antiparallel configuration, suggesting that the two configurations are, close enough in energy for subtle sequence changes to have important, structural consequences. We present a structural analysis of the small, changes to the helix register and side-chain conformations that, accommodate the two configurations and have supplemented these results, using solution studies and a molecular dynamics energetic analysis using a, replica exchange methodology. Considering the previous examples of, structural nonspecificity in coiled-coil peptides, the findings reported, here not only emphasize the predisposition of the coiled-coil motif to, adopt multiple configurations but also call attention to the associated, risk that observed crytstal structures may not represent the only (or even, the major) species present in solution.
+A detailed understanding of the mechanisms by which particular amino acid sequences can give rise to more than one folded structure, such as for proteins that undergo large conformational changes or misfolding, is a long-standing objective of protein chemistry. Here, we describe the crystal structures of a single coiled-coil peptide in distinct parallel and antiparallel tetrameric configurations and further describe the parallel or antiparallel crystal structures of several related peptide sequences; the antiparallel tetrameric assemblies represent the first crystal structures of GCN4-derived peptides exhibiting such a configuration. Intriguingly, substitution of a single solvent-exposed residue enabled the parallel coiled-coil tetramer GCN4-pLI to populate the antiparallel configuration, suggesting that the two configurations are close enough in energy for subtle sequence changes to have important structural consequences. We present a structural analysis of the small changes to the helix register and side-chain conformations that accommodate the two configurations and have supplemented these results using solution studies and a molecular dynamics energetic analysis using a replica exchange methodology. Considering the previous examples of structural nonspecificity in coiled-coil peptides, the findings reported here not only emphasize the predisposition of the coiled-coil motif to adopt multiple configurations but also call attention to the associated risk that observed crytstal structures may not represent the only (or even the major) species present in solution.
 ==About this Structure==
-W5H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W5H OCA].
+W5H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W5H OCA].
 ==Reference==
 Coiled coils at the edge of configurational heterogeneity. Structural analyses of parallel and antiparallel homotetrameric coiled coils reveal configurational sensitivity to a single solvent-exposed amino acid substitution., Yadav MK, Leman LJ, Price DJ, Brooks CL 3rd, Stout CD, Ghadiri MR, Biochemistry. 2006 Apr 11;45(14):4463-73. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16584182 16584182]
 [[Category: Single protein]]
-[[Category: Ghadiri, M.R.]]
+[[Category: Ghadiri, M R.]]
 [[Category: Leman, L.]]
-[[Category: Stout, C.D.]]
+[[Category: Stout, C D.]]
-[[Category: Yadav, M.K.]]
+[[Category: Yadav, M K.]]
 [[Category: antiparallel four helix bundle]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 05:14:05 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:40:40 2008''