Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1782391043921018880 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4577960 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT watkinsandrewm proteinproteininteractionsmediatedbyhelicaltertiarystructuremotifs AT wuomichaelg proteinproteininteractionsmediatedbyhelicaltertiarystructuremotifs AT aroraparamjits proteinproteininteractionsmediatedbyhelicaltertiarystructuremotifs |