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A Heterospecific Leucine Zipper Tetramer

Protein-protein interactions dictate the assembly of the macromolecular complexes essential for functional networks and cellular behavior. Elucidating principles of molecular recognition governing important interfaces such as coiled coils is a challenging goal for structural and systems biology. We...

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Detalles Bibliográficos
Autores principales: Deng, Yiqun, Liu, Jie, Zheng, Qi, Li, Qunnu, Kallenbach, Neville R., Lu, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111190/
https://www.ncbi.nlm.nih.gov/pubmed/18804028
http://dx.doi.org/10.1016/j.chembiol.2008.07.008
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author Deng, Yiqun
Liu, Jie
Zheng, Qi
Li, Qunnu
Kallenbach, Neville R.
Lu, Min
author_facet Deng, Yiqun
Liu, Jie
Zheng, Qi
Li, Qunnu
Kallenbach, Neville R.
Lu, Min
author_sort Deng, Yiqun
collection PubMed
description Protein-protein interactions dictate the assembly of the macromolecular complexes essential for functional networks and cellular behavior. Elucidating principles of molecular recognition governing important interfaces such as coiled coils is a challenging goal for structural and systems biology. We report here that two valine-containing mutants of the GCN4 leucine zipper that fold individually as four-stranded coiled coils associate preferentially in mixtures to form an antiparallel, heterotetrameric structure. X-ray crystallographic analysis reveals that the coinciding hydrophobic interfaces of the hetero- and homotetramers differ in detail, explaining their partnering and structural specificity. Equilibrium disulfide exchange and thermal denaturation experiments show that the 50-fold preference for heterospecificity results from a combination of preferential packing and hydrophobicity. The extent of preference is sensitive to the side chains comprising the interface. Thus, heterotypic versus homotypic interaction specificity in coiled coils reflects a delicate balance in complementarity of shape and chemistry of the participating side chains.
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spelling pubmed-71111902020-04-02 A Heterospecific Leucine Zipper Tetramer Deng, Yiqun Liu, Jie Zheng, Qi Li, Qunnu Kallenbach, Neville R. Lu, Min Chem Biol Article Protein-protein interactions dictate the assembly of the macromolecular complexes essential for functional networks and cellular behavior. Elucidating principles of molecular recognition governing important interfaces such as coiled coils is a challenging goal for structural and systems biology. We report here that two valine-containing mutants of the GCN4 leucine zipper that fold individually as four-stranded coiled coils associate preferentially in mixtures to form an antiparallel, heterotetrameric structure. X-ray crystallographic analysis reveals that the coinciding hydrophobic interfaces of the hetero- and homotetramers differ in detail, explaining their partnering and structural specificity. Equilibrium disulfide exchange and thermal denaturation experiments show that the 50-fold preference for heterospecificity results from a combination of preferential packing and hydrophobicity. The extent of preference is sensitive to the side chains comprising the interface. Thus, heterotypic versus homotypic interaction specificity in coiled coils reflects a delicate balance in complementarity of shape and chemistry of the participating side chains. Elsevier Ltd. 2008-09-22 2008-09-19 /pmc/articles/PMC7111190/ /pubmed/18804028 http://dx.doi.org/10.1016/j.chembiol.2008.07.008 Text en Copyright © 2008 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Deng, Yiqun
Liu, Jie
Zheng, Qi
Li, Qunnu
Kallenbach, Neville R.
Lu, Min
A Heterospecific Leucine Zipper Tetramer
title A Heterospecific Leucine Zipper Tetramer
title_full A Heterospecific Leucine Zipper Tetramer
title_fullStr A Heterospecific Leucine Zipper Tetramer
title_full_unstemmed A Heterospecific Leucine Zipper Tetramer
title_short A Heterospecific Leucine Zipper Tetramer
title_sort heterospecific leucine zipper tetramer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111190/
https://www.ncbi.nlm.nih.gov/pubmed/18804028
http://dx.doi.org/10.1016/j.chembiol.2008.07.008
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