1zbn: Difference between revisions

Revision as of 17:13, 21 February 2008

Solution structure of BIV TAR hairpin complexed to JDV Tat arginine-rich motif

OverviewOverview

An arginine-rich peptide from the Jembrana disease virus (JDV) Tat protein is a structural "chameleon" that binds bovine immunodeficiency virus (BIV) or HIV TAR RNAs in two different binding modes, with an affinity for BIV TAR even higher than the cognate BIV peptide. We determined the NMR structure of the JDV Tat-BIV TAR high-affinity complex and found that the C-terminal tyrosine in JDV Tat forms a network of inter- and intramolecular hydrogen bonding and stacking interactions that simultaneously stabilize the beta-hairpin conformation of the peptide and a base triple in the RNA. A neighboring histidine also appears to help stabilize the peptide conformation. Induced fit binding is recurrent in protein-protein and protein-nucleic acid interactions, and the JDV Tat complex demonstrates how high affinity can be achieved not only by optimization of the binding interface but also by inducing new intramolecular contacts that stabilize each binding partner. Comparison to the cognate BIV Tat peptide-TAR complex shows how such a costabilization mechanism can evolve with only small changes to the peptide sequence. In addition, the bound structure of BIV TAR in the chameleon peptide complex is strikingly similar to the bound conformation of HIV TAR, suggesting new strategies for the development of HIV TAR binding molecules.

About this StructureAbout this Structure

1ZBN is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

ReferenceReference

A single intermolecular contact mediates intramolecular stabilization of both RNA and protein., Calabro V, Daugherty MD, Frankel AD, Proc Natl Acad Sci U S A. 2005 May 10;102(19):6849-54. Epub 2005 Apr 27. PMID:15857951

Page seeded by OCA on Thu Feb 21 16:13:58 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1zbn.gif|left|200px]]<br /><applet load="1zbn" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1zbn.gif|left|200px]]<br /><applet load="1zbn" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1zbn" />
 '''Solution structure of BIV TAR hairpin complexed to JDV Tat arginine-rich motif'''<br />
 ==Overview==
-An arginine-rich peptide from the Jembrana disease virus (JDV) Tat protein, is a structural "chameleon" that binds bovine immunodeficiency virus (BIV), or HIV TAR RNAs in two different binding modes, with an affinity for BIV, TAR even higher than the cognate BIV peptide. We determined the NMR, structure of the JDV Tat-BIV TAR high-affinity complex and found that the, C-terminal tyrosine in JDV Tat forms a network of inter- and, intramolecular hydrogen bonding and stacking interactions that, simultaneously stabilize the beta-hairpin conformation of the peptide and, a base triple in the RNA. A neighboring histidine also appears to help, stabilize the peptide conformation. Induced fit binding is recurrent in, protein-protein and protein-nucleic acid interactions, and the JDV Tat, complex demonstrates how high affinity can be achieved not only by, optimization of the binding interface but also by inducing new, intramolecular contacts that stabilize each binding partner. Comparison to, the cognate BIV Tat peptide-TAR complex shows how such a costabilization, mechanism can evolve with only small changes to the peptide sequence. In, addition, the bound structure of BIV TAR in the chameleon peptide complex, is strikingly similar to the bound conformation of HIV TAR, suggesting new, strategies for the development of HIV TAR binding molecules.
+An arginine-rich peptide from the Jembrana disease virus (JDV) Tat protein is a structural "chameleon" that binds bovine immunodeficiency virus (BIV) or HIV TAR RNAs in two different binding modes, with an affinity for BIV TAR even higher than the cognate BIV peptide. We determined the NMR structure of the JDV Tat-BIV TAR high-affinity complex and found that the C-terminal tyrosine in JDV Tat forms a network of inter- and intramolecular hydrogen bonding and stacking interactions that simultaneously stabilize the beta-hairpin conformation of the peptide and a base triple in the RNA. A neighboring histidine also appears to help stabilize the peptide conformation. Induced fit binding is recurrent in protein-protein and protein-nucleic acid interactions, and the JDV Tat complex demonstrates how high affinity can be achieved not only by optimization of the binding interface but also by inducing new intramolecular contacts that stabilize each binding partner. Comparison to the cognate BIV Tat peptide-TAR complex shows how such a costabilization mechanism can evolve with only small changes to the peptide sequence. In addition, the bound structure of BIV TAR in the chameleon peptide complex is strikingly similar to the bound conformation of HIV TAR, suggesting new strategies for the development of HIV TAR binding molecules.
 ==About this Structure==
-ZBN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZBN OCA].
+ZBN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZBN OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Protein complex]]
 [[Category: Calabro, V.]]
-[[Category: Daugherty, M.D.]]
+[[Category: Daugherty, M D.]]
-[[Category: Frankel, A.D.]]
+[[Category: Frankel, A D.]]
 [[Category: rna-peptide complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 07:22:11 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:13:58 2008''