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PMID: 29424691 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Pi-Pi contacts are an overlooked protein feature relevant to phase separation.

eLife ·Vol. 7 ·2018-00-09

Vernon RM, Chong PA, Tsang B, Kim TH, Bah A, Farber P, Lin H, Forman-Kay JD

Abstract

Protein phase separation is implicated in formation of membraneless organelles, signaling puncta and the nuclear pore. Multivalent interactions of modular binding domains and their target motifs can drive phase separation. However, forces promoting the more common phase separation of intrinsically disordered regions are less understood, with suggested roles for multivalent cation-pi, pi-pi, and charge interactions and the hydrophobic effect. Known phase-separating proteins are enriched in pi-orbital containing residues and thus we analyzed pi-interactions in folded proteins. We found that pi-pi interactions involving non-aromatic groups are widespread, underestimated by force-fields used in structure calculations and correlated with solvation and lack of regular secondary structure, properties associated with disordered regions. We present a phase separation predictive algorithm based on pi interaction frequency, highlighting proteins involved in biomaterials and RNA processing.

Keywords
bioinformatics computational biology human molecular biophysics pi interactions prediction protein interactions protein phase separation protein structure structural biology systems biology
MeSH Terms
Hydrophobic and Hydrophilic Interactions Intrinsically Disordered Proteins/chemistry,metabolism Organelles/chemistry,metabolism Protein Binding Protein Folding Static Electricity
Chemicals
Intrinsically Disordered Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Vernon Robert McCoy
Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada.
Chong Paul Andrew
Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada.
Tsang Brian
Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada. | Department of Biochemistry, University of Toronto, Toronto, Canada.
Kim Tae Hun
Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada.
Bah Alaji
Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada.
Farber Patrick
Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada.
Lin Hong
Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada.
Forman-Kay Julie Deborah ORCID
Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada. | Department of Biochemistry, University of Toronto, Toronto, Canada.
Conflict of Interest

RV, PC, BT, TK, AB, PF, HL, JF No competing interests declared

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Article Info
Journal
eLife
Abbr.
Elife
ISSN
2050-084X
DOI
10.7554/eLife.31486
Published
2018-00-09
Epub
2018-00-09
Language
English
Region
England
NLM ID
101579614
PMCID
PMC5847340
Grants
CIHR · 114985 · Canada
External Links
PubMed source DOI: 10.7554/eLife.31486 PMC Full Text View journal details
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