Binding of two intrinsically disordered peptides to a multi-specific protein: a combined Monte Carlo and molecular dynamics study
(2012) In PLoS Computational Biology 8(9).- Abstract
- The unique ability of intrinsically disordered proteins (IDPs) to fold upon binding to partner molecules makes them functionally well-suited for cellular communication networks. For example, the folding-binding of different IDP sequences onto the same surface of an ordered protein provides a mechanism for signaling in a many-to-one manner. Here, we study the molecular details of this signaling mechanism by applying both Molecular Dynamics and Monte Carlo methods to S100B, a calcium-modulated homodimeric protein, and two of its IDP targets, p53 and TRTK-12. Despite adopting somewhat different conformations in complex with S100B and showing no apparent sequence similarity, the two IDP targets associate in virtually the same manner. As free... (More)
- The unique ability of intrinsically disordered proteins (IDPs) to fold upon binding to partner molecules makes them functionally well-suited for cellular communication networks. For example, the folding-binding of different IDP sequences onto the same surface of an ordered protein provides a mechanism for signaling in a many-to-one manner. Here, we study the molecular details of this signaling mechanism by applying both Molecular Dynamics and Monte Carlo methods to S100B, a calcium-modulated homodimeric protein, and two of its IDP targets, p53 and TRTK-12. Despite adopting somewhat different conformations in complex with S100B and showing no apparent sequence similarity, the two IDP targets associate in virtually the same manner. As free chains, both target sequences remain flexible and sample their respective bound, natively alpha-helical states to a small extent. Association occurs through an intermediate state in the periphery of the S100B binding pocket, stabilized by nonnative interactions which are either hydrophobic or electrostatic in nature. Our results highlight the importance of overall physical properties of IDP segments, such as net charge or presence of strongly hydrophobic amino acids, for molecular recognition via coupled folding-binding. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3161270
- author
- Staneva, Iskra ; Huang, Yongqi ; Liu, Zhirong and Wallin, Stefan LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Monte Carlo, Molecular Dynamics, protein, binding
- in
- PLoS Computational Biology
- volume
- 8
- issue
- 9
- article number
- e1002682
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000309510900019
- pmid:23028280
- scopus:84866944317
- pmid:23028280
- ISSN
- 1553-7358
- DOI
- 10.1371/journal.pcbi.1002682
- language
- English
- LU publication?
- yes
- id
- 010c9aca-cd45-4165-9e36-b148b0b3bb10 (old id 3161270)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23028280?dopt=Abstract
- date added to LUP
- 2016-04-04 08:10:24
- date last changed
- 2024-01-12 03:56:48
@article{010c9aca-cd45-4165-9e36-b148b0b3bb10,
abstract = {{The unique ability of intrinsically disordered proteins (IDPs) to fold upon binding to partner molecules makes them functionally well-suited for cellular communication networks. For example, the folding-binding of different IDP sequences onto the same surface of an ordered protein provides a mechanism for signaling in a many-to-one manner. Here, we study the molecular details of this signaling mechanism by applying both Molecular Dynamics and Monte Carlo methods to S100B, a calcium-modulated homodimeric protein, and two of its IDP targets, p53 and TRTK-12. Despite adopting somewhat different conformations in complex with S100B and showing no apparent sequence similarity, the two IDP targets associate in virtually the same manner. As free chains, both target sequences remain flexible and sample their respective bound, natively alpha-helical states to a small extent. Association occurs through an intermediate state in the periphery of the S100B binding pocket, stabilized by nonnative interactions which are either hydrophobic or electrostatic in nature. Our results highlight the importance of overall physical properties of IDP segments, such as net charge or presence of strongly hydrophobic amino acids, for molecular recognition via coupled folding-binding.}},
author = {{Staneva, Iskra and Huang, Yongqi and Liu, Zhirong and Wallin, Stefan}},
issn = {{1553-7358}},
keywords = {{Monte Carlo; Molecular Dynamics; protein; binding}},
language = {{eng}},
number = {{9}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS Computational Biology}},
title = {{Binding of two intrinsically disordered peptides to a multi-specific protein: a combined Monte Carlo and molecular dynamics study}},
url = {{http://dx.doi.org/10.1371/journal.pcbi.1002682}},
doi = {{10.1371/journal.pcbi.1002682}},
volume = {{8}},
year = {{2012}},
}