Fine-tuning function: correlation of hinge domain interactions with functional distinctions between LacI and PurR

Protein Science : a Publication of the Protein Society
Liskin Swint-KruseK S Matthews

Abstract

LacI and PurR are highly homologous proteins. Their functional units are homodimers, with an N-terminal DNA binding domain that comprises the helix-turn-helix (HTH), N-linker, and hinge regions from both monomers. Hinge structural changes are known to occur upon DNA dissociation but are difficult to monitor experimentally. The initial steps of hinge unfolding were therefore examined using molecular dynamics simulations, utilizing a truncated, chimeric protein comprising the LacI HTH/N-linker and PurR hinge. A terminal Gly-Cys-Gly was added to allow "dimerization" through disulfide bond formation. Simulations indicate that differences in LacI and PurR hinge primary sequence affect the quaternary structure of the hinge x hinge' interface. However, these alternate hinge orientations would be sterically restricted by the core domain. These results prompted detailed comparison of recently available DNA-bound structures for LacI and truncated LacI(1-62) with the PurR structure. Examination revealed that different N-linker and hinge contacts to the core domain of the partner monomer (which binds effector molecule) affect the juxtapositions of the HTH, N-linker, and hinge regions in the DNA binding domain. In addition, the two full-len...Continue Reading

References

Aug 24, 1978·Nature·P J Farabaugh
Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Jul 1, 1986·Biochemistry·P A WhitsonK S Matthews
Dec 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·K BeyreutherA Klemm
Dec 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·W Gilbert, A Maxam
Nov 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·J R SadlerJ L Betz
Mar 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·A SimonsB Müller-Hill
Feb 1, 1996·Journal of Molecular Graphics·R KoradiK Wüthrich
Sep 25, 1997·Trends in Biochemical Sciences·H C PaceM Lewis
Oct 27, 1997·The Journal of Biological Chemistry·C M FalconK S Matthews
May 16, 1998·The Journal of Biological Chemistry·H XuK S Matthews
Jun 17, 1998·Nature Structural Biology·D N ArvidsonR G Brennan
Oct 31, 1998·Protein Engineering·I N Shindyalov, P E Bourne
May 13, 1999·Bioinformatics·V SobolevM Edelman
Oct 16, 1999·The Journal of Biological Chemistry·C M Falcon, K S Matthews
Dec 11, 1999·Nucleic Acids Research·A Bairoch, R Apweiler
Mar 4, 2000·Nature Structural Biology·K S MatthewsL Swint-Kruse
Mar 4, 2000·Nature Structural Biology·C E Bell, M Lewis
Feb 17, 2001·Current Opinion in Structural Biology·C E Bell, M Lewis
Feb 22, 2001·Science·J C VenterX Zhu
Mar 27, 2001·Protein Science : a Publication of the Protein Society·L Swint-KruseK Shive Matthews
May 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·C G KalodimosR Kaptein
May 25, 2001·Nature Structural Biology·D VitkupC Sander

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Citations

May 10, 2005·Biopolymers·Willy WriggersPatricia A Jennings
May 26, 2005·Bioinformatics·Liskin Swint-Kruse, Curties S Brown
Jan 5, 2014·PloS One·Sarah MeinhardtLiskin Swint-Kruse
Jul 1, 2011·Biophysical Chemistry·Sudheer TungturDorothy Beckett
Sep 28, 2015·Journal of Molecular Biology·Filipa L SousaLiskin Swint-Kruse
Oct 24, 2003·Protein Science : a Publication of the Protein Society·Terence C FlynnJianpeng Ma
Aug 18, 2004·Journal of Molecular Biology·Birgitte H Kallipolitis, Poul Valentin-Hansen
Jan 11, 2018·Protein Science : a Publication of the Protein Society·Joseph S XuKathleen S Matthews
Sep 6, 2015·The Journal of Biological Chemistry·Sarah E BondosKathleen S Matthews
Nov 30, 2018·Biopolymers·Danielle Seckfort, B Montgomery Pettitt
Oct 21, 2020·Biochemical Society Transactions·Shaun Spisak, Marc Ostermeier

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