Critical residue that promotes protein dimerization: A story of partially exposed Phe25 in 14-3-3σ

Jing Yuan Liu, Zhaomin Li, Huian Li, Jian-Ting Zhang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Many proteins exist and function as oligomers. While hydrophobic interactions have been recognized as the major driving force for oligomerization, detailed molecular mechanisms for the assembly are unknown. Here, we used 14-3-3σ as a model protein and investigated the role of hydrophobic residues at the dimeric interface using MD simulations and coimmunoprecipitations. We found that a half-exposed and half-buried residue in the interface, Phe25, plays a more important role in promoting homodimerization than the hydrophobic core residues by organizing both favorable hydrophobic and hydrophilic interactions. Phe25 is critical in packing and stabilizing hydrophobic core residues. We conclude that the structural stability of hydrophobic cores is critical for a stable homodimer complex and this stable property can be bestowed by residues outside of hydrophobic core. The important organizing activity of Phe25 for homodimerization of 14-3-3σ originates from its unique physical location, rigidity, size, and hydrophobicity. Thus, hydrophobic residues that are not deeply buried at the oligomeric interface may play important but different roles from the buried core residues and they may promote oligomerization by organizing co-operativity of core and other residues for favorable hydrophobic and electrostatic interactions.

Original languageEnglish
Pages (from-to)2612-2625
Number of pages14
JournalJournal of Chemical Information and Modeling
Volume51
Issue number10
DOIs
StatePublished - Oct 24 2011

Fingerprint

Oligomerization
Dimerization
Proteins
Hydrophobicity
interaction
Coulomb interactions
Oligomers
Rigidity
rigidity
simulation

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

Cite this

Critical residue that promotes protein dimerization : A story of partially exposed Phe25 in 14-3-3σ. / Liu, Jing Yuan; Li, Zhaomin; Li, Huian; Zhang, Jian-Ting.

In: Journal of Chemical Information and Modeling, Vol. 51, No. 10, 24.10.2011, p. 2612-2625.

Research output: Contribution to journalArticle

Liu, Jing Yuan ; Li, Zhaomin ; Li, Huian ; Zhang, Jian-Ting. / Critical residue that promotes protein dimerization : A story of partially exposed Phe25 in 14-3-3σ. In: Journal of Chemical Information and Modeling. 2011 ; Vol. 51, No. 10. pp. 2612-2625.
@article{0c8f9ea240d9423fad98b22f05b92777,
title = "Critical residue that promotes protein dimerization: A story of partially exposed Phe25 in 14-3-3σ",
abstract = "Many proteins exist and function as oligomers. While hydrophobic interactions have been recognized as the major driving force for oligomerization, detailed molecular mechanisms for the assembly are unknown. Here, we used 14-3-3σ as a model protein and investigated the role of hydrophobic residues at the dimeric interface using MD simulations and coimmunoprecipitations. We found that a half-exposed and half-buried residue in the interface, Phe25, plays a more important role in promoting homodimerization than the hydrophobic core residues by organizing both favorable hydrophobic and hydrophilic interactions. Phe25 is critical in packing and stabilizing hydrophobic core residues. We conclude that the structural stability of hydrophobic cores is critical for a stable homodimer complex and this stable property can be bestowed by residues outside of hydrophobic core. The important organizing activity of Phe25 for homodimerization of 14-3-3σ originates from its unique physical location, rigidity, size, and hydrophobicity. Thus, hydrophobic residues that are not deeply buried at the oligomeric interface may play important but different roles from the buried core residues and they may promote oligomerization by organizing co-operativity of core and other residues for favorable hydrophobic and electrostatic interactions.",
author = "Liu, {Jing Yuan} and Zhaomin Li and Huian Li and Jian-Ting Zhang",
year = "2011",
month = "10",
day = "24",
doi = "10.1021/ci200212y",
language = "English",
volume = "51",
pages = "2612--2625",
journal = "Journal of Chemical Information and Computer Sciences",
issn = "0095-2338",
publisher = "American Chemical Society",
number = "10",

}

TY - JOUR

T1 - Critical residue that promotes protein dimerization

T2 - A story of partially exposed Phe25 in 14-3-3σ

AU - Liu, Jing Yuan

AU - Li, Zhaomin

AU - Li, Huian

AU - Zhang, Jian-Ting

PY - 2011/10/24

Y1 - 2011/10/24

N2 - Many proteins exist and function as oligomers. While hydrophobic interactions have been recognized as the major driving force for oligomerization, detailed molecular mechanisms for the assembly are unknown. Here, we used 14-3-3σ as a model protein and investigated the role of hydrophobic residues at the dimeric interface using MD simulations and coimmunoprecipitations. We found that a half-exposed and half-buried residue in the interface, Phe25, plays a more important role in promoting homodimerization than the hydrophobic core residues by organizing both favorable hydrophobic and hydrophilic interactions. Phe25 is critical in packing and stabilizing hydrophobic core residues. We conclude that the structural stability of hydrophobic cores is critical for a stable homodimer complex and this stable property can be bestowed by residues outside of hydrophobic core. The important organizing activity of Phe25 for homodimerization of 14-3-3σ originates from its unique physical location, rigidity, size, and hydrophobicity. Thus, hydrophobic residues that are not deeply buried at the oligomeric interface may play important but different roles from the buried core residues and they may promote oligomerization by organizing co-operativity of core and other residues for favorable hydrophobic and electrostatic interactions.

AB - Many proteins exist and function as oligomers. While hydrophobic interactions have been recognized as the major driving force for oligomerization, detailed molecular mechanisms for the assembly are unknown. Here, we used 14-3-3σ as a model protein and investigated the role of hydrophobic residues at the dimeric interface using MD simulations and coimmunoprecipitations. We found that a half-exposed and half-buried residue in the interface, Phe25, plays a more important role in promoting homodimerization than the hydrophobic core residues by organizing both favorable hydrophobic and hydrophilic interactions. Phe25 is critical in packing and stabilizing hydrophobic core residues. We conclude that the structural stability of hydrophobic cores is critical for a stable homodimer complex and this stable property can be bestowed by residues outside of hydrophobic core. The important organizing activity of Phe25 for homodimerization of 14-3-3σ originates from its unique physical location, rigidity, size, and hydrophobicity. Thus, hydrophobic residues that are not deeply buried at the oligomeric interface may play important but different roles from the buried core residues and they may promote oligomerization by organizing co-operativity of core and other residues for favorable hydrophobic and electrostatic interactions.

UR - http://www.scopus.com/inward/record.url?scp=80054890115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054890115&partnerID=8YFLogxK

U2 - 10.1021/ci200212y

DO - 10.1021/ci200212y

M3 - Article

C2 - 21870863

AN - SCOPUS:80054890115

VL - 51

SP - 2612

EP - 2625

JO - Journal of Chemical Information and Computer Sciences

JF - Journal of Chemical Information and Computer Sciences

SN - 0095-2338

IS - 10

ER -