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Protein–Protein Interactions Mediated by Helical Tertiary Structure Motifs

[Image: see text] The modulation of protein–protein interactions (PPIs) by means of creating or stabilizing secondary structure conformations is a rapidly growing area of research. Recent success in the inhibition of difficult PPIs by secondary structure mimetics also points to potential limitations...

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Autores principales: Watkins, Andrew M., Wuo, Michael G., Arora, Paramjit S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2015
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577960/
https://www.ncbi.nlm.nih.gov/pubmed/26302018
http://dx.doi.org/10.1021/jacs.5b05527
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author Watkins, Andrew M.
Wuo, Michael G.
Arora, Paramjit S.
author_facet Watkins, Andrew M.
Wuo, Michael G.
Arora, Paramjit S.
author_sort Watkins, Andrew M.
collection PubMed
description [Image: see text] The modulation of protein–protein interactions (PPIs) by means of creating or stabilizing secondary structure conformations is a rapidly growing area of research. Recent success in the inhibition of difficult PPIs by secondary structure mimetics also points to potential limitations, because often, specific cases require tertiary structure mimetics. To streamline protein structure-based inhibitor design, we have previously described the examination of protein complexes in the Protein Data Bank where α-helices or β-strands form critical contacts. Here, we examined coiled coils and helix bundles that mediate complex formation to create a platform for the discovery of potential tertiary structure mimetics. Though there has been extensive analysis of coiled coil motifs, the interactions between pre-formed coiled coils and globular proteins have not been systematically analyzed. This article identifies critical features of these helical interfaces with respect to coiled coil and other helical PPIs. We expect the analysis to prove useful for the rational design of modulators of this fundamental class of protein assemblies.
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spelling pubmed-45779602015-09-30 Protein–Protein Interactions Mediated by Helical Tertiary Structure Motifs Watkins, Andrew M. Wuo, Michael G. Arora, Paramjit S. J Am Chem Soc [Image: see text] The modulation of protein–protein interactions (PPIs) by means of creating or stabilizing secondary structure conformations is a rapidly growing area of research. Recent success in the inhibition of difficult PPIs by secondary structure mimetics also points to potential limitations, because often, specific cases require tertiary structure mimetics. To streamline protein structure-based inhibitor design, we have previously described the examination of protein complexes in the Protein Data Bank where α-helices or β-strands form critical contacts. Here, we examined coiled coils and helix bundles that mediate complex formation to create a platform for the discovery of potential tertiary structure mimetics. Though there has been extensive analysis of coiled coil motifs, the interactions between pre-formed coiled coils and globular proteins have not been systematically analyzed. This article identifies critical features of these helical interfaces with respect to coiled coil and other helical PPIs. We expect the analysis to prove useful for the rational design of modulators of this fundamental class of protein assemblies. American Chemical Society 2015-08-24 2015-09-16 /pmc/articles/PMC4577960/ /pubmed/26302018 http://dx.doi.org/10.1021/jacs.5b05527 Text en Copyright © 2015 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Watkins, Andrew M.
Wuo, Michael G.
Arora, Paramjit S.
Protein–Protein Interactions Mediated by Helical Tertiary Structure Motifs
title Protein–Protein Interactions Mediated by Helical Tertiary Structure Motifs
title_full Protein–Protein Interactions Mediated by Helical Tertiary Structure Motifs
title_fullStr Protein–Protein Interactions Mediated by Helical Tertiary Structure Motifs
title_full_unstemmed Protein–Protein Interactions Mediated by Helical Tertiary Structure Motifs
title_short Protein–Protein Interactions Mediated by Helical Tertiary Structure Motifs
title_sort protein–protein interactions mediated by helical tertiary structure motifs
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577960/
https://www.ncbi.nlm.nih.gov/pubmed/26302018
http://dx.doi.org/10.1021/jacs.5b05527
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