Abstract While an extensive body of knowledge has accumulated on the structures of transcription factors, DNA and their complexes from both NMR and crystallography, much less is known at a molecular level regarding the mechanisms whereby transcription factors locate their specific DNA target site within an overwhelming sea of non-specific DNA sites. Indirect kinetic data suggested that three processes are involved in the search procedure: jumping by dissociation of the protein from the DNA followed by re-association at another site, direct transfer from one DNA molecule or segment to another, and one-dimensional sliding. In this brief perspective I summarize recent NMR developments from our laboratory that have permitted direct characterization of the species and molecular mechanisms involved in the target search process, including the detection of highly transient sparsely-populated states. The main tool in these studies involves the application of paramagnetic relaxation enhancement, supplemented by z-exchange spectroscopy, lineshape analysis and residual dipolar couplings. These studies led to the first direct demonstration of rotation-coupled sliding of a protein along the DNA and the direct transfer of a protein from one DNA molecule to another without dissociating into free solution.
Content Type Journal Article
Category Perspective
Pages 1-11
DOI 10.1007/s10858-011-9555-8
Authors
G. Marius Clore, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 02892-0520, USA
Intra- and intermolecular translocation of the bi-domain transcription factor Oct1 characterized by liquid crystal and paramagnetic NMR.
Intra- and intermolecular translocation of the bi-domain transcription factor Oct1 characterized by liquid crystal and paramagnetic NMR.
Intra- and intermolecular translocation of the bi-domain transcription factor Oct1 characterized by liquid crystal and paramagnetic NMR.
Proc Natl Acad Sci U S A. 2011 May 31;108(22):E169-76
Authors: Takayama Y, Clore GM
Abstract
The intra- and intermolecular translocation processes whereby the bi-domain transcription factor Oct1 searches for its specific DNA target site have been investigated by...
nmrlearner
Journal club
1
08-25-2011 07:02 AM
Exploring translocation of proteins on DNA by NMR.
Exploring translocation of proteins on DNA by NMR.
Exploring translocation of proteins on DNA by NMR.
J Biomol NMR. 2011 Aug 17;
Authors: Marius Clore G
Abstract
While an extensive body of knowledge has accumulated on the structures of transcription factors, DNA and their complexes from both NMR and crystallography, much less is known at a molecular level regarding the mechanisms whereby transcription factors locate their specific DNA target site within an overwhelming sea of non-specific DNA sites. Indirect kinetic data suggested that...
nmrlearner
Journal club
0
08-19-2011 02:56 PM
Intra- and intermolecular translocation of the bi-domain transcription factor Oct1 characterized by liquid crystal and paramagnetic NMR [Biophysics and Computational Biology]
Intra- and intermolecular translocation of the bi-domain transcription factor Oct1 characterized by liquid crystal and paramagnetic NMR
Takayama, Y., Clore, G. M....
Date: 2011-05-31
The intra- and intermolecular translocation processes whereby the bi-domain transcription factor Oct1 searches for its specific DNA target site have been investigated by residual dipolar coupling (RDC) and paramagnetic relaxation enhancement (PRE) measurements. The RDC data show that the orientation of the POUS and POUHD domains of Oct1 relative to the long axis of the DNA is the same for specific and...
nmrlearner
Journal club
0
05-31-2011 11:41 PM
Exploring NMR ensembles of calcium binding proteins: perspectives to design inhibitors of protein-protein interactions.
Exploring NMR ensembles of calcium binding proteins: perspectives to design inhibitors of protein-protein interactions.
Exploring NMR ensembles of calcium binding proteins: perspectives to design inhibitors of protein-protein interactions.
BMC Struct Biol. 2011 May 12;11(1):24
Authors: Isvoran A, Badel A, Craescu CT, Miron S, Miteva MA
ABSTRACT: BACKGROUND: Disrupting protein-protein interactions by small organic molecules is nowadays a promising strategy employed to block protein targets involved in different pathologies. However, structural...
nmrlearner
Journal club
0
05-17-2011 06:21 PM
Exploring NMR ensembles of calcium binding proteins: perspectives to design ... - 7thSpace Interactive (press release)
Exploring NMR ensembles of calcium binding proteins: perspectives to design ... - 7thSpace Interactive (press release)
<img alt="" height="1" width="1" />
Exploring NMR ensembles of calcium binding proteins: perspectives to design ...
7thSpace Interactive (press release)
We employed several scoring methods in order to find the best protein conformations. Our results show that docking on NMR structures of calmodulin and centrin can be very helpful to take into account conformational changes occurring at protein-protein ...
Read here
nmrlearner
Online News
0
05-13-2011 07:41 AM
[NMR paper] Exploring surfaces and cavities in lipoxygenase and other proteins by hyperpolarized
Exploring surfaces and cavities in lipoxygenase and other proteins by hyperpolarized xenon-129 NMR.
Related Articles Exploring surfaces and cavities in lipoxygenase and other proteins by hyperpolarized xenon-129 NMR.
J Am Chem Soc. 1999 Oct 13;121(40):9370-7
Authors: Bowers CR, Storhaug V, Webster CE, Bharatam J, Cottone A, Gianna R, Betsey K, Gaffney BJ
This paper presents an exploratory study of the binding interactions of xenon with the surface of several different proteins in the solution and solid states using both conventional and...
nmrlearner
Journal club
0
11-18-2010 08:31 PM
NMR Studies of Translocation of the Zif268 Protein between Its Target DNA Sites
NMR Studies of Translocation of the Zif268 Protein between Its Target DNA Sites
http://pubs.acs.org//appl/literatum/publisher/achs/journals/content/bichaw/0/bichaw.ahead-of-print/bi100962h/aop/images/medium/bi-2010-00962h_0005.gifBiochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable).
More...
nmrlearner
Journal club
0
08-31-2010 10:50 PM
NMR studies of translocation of the Zif268 protein between its target DNA sites.
NMR studies of translocation of the Zif268 protein between its target DNA sites.
Related Articles NMR studies of translocation of the Zif268 protein between its target DNA sites.
Biochemistry. 2010 Aug 19;
Authors: Takayama Y, Sahu D, Iwahara J
Zif268 is a zinc-finger protein containing three Cys2-His2-type zinc-finger domains that bind the target DNA sequence GCGTGGGCG in a cooperative manner. In this work, we characterized translocation of the Zif268 protein between its target DNA sites using NMR spectroscopy. The residual dipolar coupling...
Exploring translocation of proteins on DNA by NMR
Linear Mode
