View source for 2xgd


==Crystal structure of a designed homodimeric variant T-A(L)A(L) of the tetracycline repressor==
<StructureSection load='2xgd' size='340' side='right'caption='[[2xgd]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2xgd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XGD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xgd OCA], [https://pdbe.org/2xgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xgd RCSB], [https://www.ebi.ac.uk/pdbsum/2xgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xgd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TETR4_ECOLX TETR4_ECOLX] TetR is the repressor of the tetracycline resistance element; its N-terminal region forms a helix-turn-helix structure and binds DNA. Binding of tetracycline to TetR reduces the repressor affinity for the tetracycline resistance gene (tetA) promoter operator sites.[https://www.uniprot.org/uniprot/TETR2_ECOLX TETR2_ECOLX] TetR is the repressor of the tetracycline resistance element; its N-terminal region forms a helix-turn-helix structure and binds DNA. Binding of tetracycline to TetR reduces the repressor affinity for the tetracycline resistance gene (tetA) promoter operator sites.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xg/2xgd_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2xgd ConSurf].
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== Publication Abstract from PubMed ==
The specificity and selectivity of protein-protein interactions are of central importance for many biological processes, including signal transduction and transcription control. We used the in-house side-chain packing program MUMBO to computationally design a chain-specific heterodimeric variant of the bacterial transcription regulator tetracycline repressor (TetR), called T-A(A)B. Our goal was to engineer two different TetR chain variants, A and B, that no longer interact as AA or BB homodimers but selectively recombine to form heterodimers. Although 56 residues from each chain contribute to a dimer interface as large as 2200 A(2) in wild-type TetR, the substitution of only three residues in one chain and two residues in a second chain sufficed for generating specificity in a T-A(A)B heterodimer variant. The design was corroborated in vivo by a cell-based transcription assay, and in vitro by CD spectroscopy and X-ray crystallography. Crystal structure analyses showed that while selectivity in the B chain is achieved entirely through van der Waals repulsion, the best selectivity in the A chain is obtained for the variant with the lowest number of atoms in the interface, thus possibly leading to underpacking of the dimer interface. This results in a marked decrease in thermal stability and a drastic reduction in the solubility of the T-A(A)A(A) homodimer in comparison to the designed T-A(A)B heterodimer variant.

Computational Design of a Chain-Specific Tetracycline Repressor Heterodimer.,Stiebritz MT, Wengrzik S, Klein DL, Richter JP, Srebrzynski A, Weiler S, Muller YA J Mol Biol. 2010 Sep 10. PMID:20816982<ref>PMID:20816982</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Tetracycline repressor protein 3D structures|Tetracycline repressor protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Muller YA]]
[[Category: Richter JP]]
[[Category: Stiebritz MT]]
[[Category: Wengrzik S]]