RING domains functioning as E3 ligases reveal distinct structural features: A molecular dynamics simulation study

Jian Hua Zhao, Ching Tao Yang, Josephine W. Wu, Wei Bor Tsai, Hsin Yi Lin, Hsu Wei Fang, Yih Ho, Hsuan Liang Liu

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

RING domain, a cysteine-rich motif that chelates two zinc ions, has been shown to regulate many biological processes such as mediating a crucial step in the ubiquitinylation pathway. In order to investigate the distinct structural features for the RING domains functioning as E3 ligases, several molecular dynamics simulations involving the c-Cbl, CNOT4 (with E3 ligase function), and p44 (no E3 ligase function) RING domains were conducted in this study. Our results reveal that the structural stability of the recognition site is a basic requirement for the RING domains functioning as E3 ligases. The structural stability of the recognition site is maintained by the hydrophobic core and hydrogen bonding network. Another important structural feature of the RING domains functioning as E3 ligases is the stable distances between the recognition site and the zinc ion binding sites S1 and S2. Moreover, the RING domains functioning as E3 ligases seem to exhibit lower β stability due to the higher proportion of proline residues in their sequences. However, no significant difference of the other secondary (α and turn) and the tertiary structural stabilities can be observed among these three RING domains.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalJournal of Biomolecular Structure and Dynamics
Volume26
Issue number1
Publication statusPublished - Aug 2008

Fingerprint

Ubiquitin-Protein Ligases
Molecular Dynamics Simulation
Zinc
Ions
Biological Phenomena
Hydrogen Bonding
Proline
Cysteine
Binding Sites

Keywords

  • c-Cbl
  • CNOT4
  • Molecular dynamics simulations
  • p44
  • Proteasome
  • Recognition site
  • RING domain
  • Ubiquitinylation

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

RING domains functioning as E3 ligases reveal distinct structural features : A molecular dynamics simulation study. / Zhao, Jian Hua; Yang, Ching Tao; Wu, Josephine W.; Tsai, Wei Bor; Lin, Hsin Yi; Fang, Hsu Wei; Ho, Yih; Liu, Hsuan Liang.

In: Journal of Biomolecular Structure and Dynamics, Vol. 26, No. 1, 08.2008, p. 65-73.

Research output: Contribution to journalArticle

Zhao, Jian Hua ; Yang, Ching Tao ; Wu, Josephine W. ; Tsai, Wei Bor ; Lin, Hsin Yi ; Fang, Hsu Wei ; Ho, Yih ; Liu, Hsuan Liang. / RING domains functioning as E3 ligases reveal distinct structural features : A molecular dynamics simulation study. In: Journal of Biomolecular Structure and Dynamics. 2008 ; Vol. 26, No. 1. pp. 65-73.
@article{da7f00d27a2f4f5b8713b36b9adb12e4,
title = "RING domains functioning as E3 ligases reveal distinct structural features: A molecular dynamics simulation study",
abstract = "RING domain, a cysteine-rich motif that chelates two zinc ions, has been shown to regulate many biological processes such as mediating a crucial step in the ubiquitinylation pathway. In order to investigate the distinct structural features for the RING domains functioning as E3 ligases, several molecular dynamics simulations involving the c-Cbl, CNOT4 (with E3 ligase function), and p44 (no E3 ligase function) RING domains were conducted in this study. Our results reveal that the structural stability of the recognition site is a basic requirement for the RING domains functioning as E3 ligases. The structural stability of the recognition site is maintained by the hydrophobic core and hydrogen bonding network. Another important structural feature of the RING domains functioning as E3 ligases is the stable distances between the recognition site and the zinc ion binding sites S1 and S2. Moreover, the RING domains functioning as E3 ligases seem to exhibit lower β stability due to the higher proportion of proline residues in their sequences. However, no significant difference of the other secondary (α and turn) and the tertiary structural stabilities can be observed among these three RING domains.",
keywords = "c-Cbl, CNOT4, Molecular dynamics simulations, p44, Proteasome, Recognition site, RING domain, Ubiquitinylation",
author = "Zhao, {Jian Hua} and Yang, {Ching Tao} and Wu, {Josephine W.} and Tsai, {Wei Bor} and Lin, {Hsin Yi} and Fang, {Hsu Wei} and Yih Ho and Liu, {Hsuan Liang}",
year = "2008",
month = "8",
language = "English",
volume = "26",
pages = "65--73",
journal = "Journal of Biomolecular Structure and Dynamics",
issn = "0739-1102",
publisher = "Adenine Press",
number = "1",

}

TY - JOUR

T1 - RING domains functioning as E3 ligases reveal distinct structural features

T2 - A molecular dynamics simulation study

AU - Zhao, Jian Hua

AU - Yang, Ching Tao

AU - Wu, Josephine W.

AU - Tsai, Wei Bor

AU - Lin, Hsin Yi

AU - Fang, Hsu Wei

AU - Ho, Yih

AU - Liu, Hsuan Liang

PY - 2008/8

Y1 - 2008/8

N2 - RING domain, a cysteine-rich motif that chelates two zinc ions, has been shown to regulate many biological processes such as mediating a crucial step in the ubiquitinylation pathway. In order to investigate the distinct structural features for the RING domains functioning as E3 ligases, several molecular dynamics simulations involving the c-Cbl, CNOT4 (with E3 ligase function), and p44 (no E3 ligase function) RING domains were conducted in this study. Our results reveal that the structural stability of the recognition site is a basic requirement for the RING domains functioning as E3 ligases. The structural stability of the recognition site is maintained by the hydrophobic core and hydrogen bonding network. Another important structural feature of the RING domains functioning as E3 ligases is the stable distances between the recognition site and the zinc ion binding sites S1 and S2. Moreover, the RING domains functioning as E3 ligases seem to exhibit lower β stability due to the higher proportion of proline residues in their sequences. However, no significant difference of the other secondary (α and turn) and the tertiary structural stabilities can be observed among these three RING domains.

AB - RING domain, a cysteine-rich motif that chelates two zinc ions, has been shown to regulate many biological processes such as mediating a crucial step in the ubiquitinylation pathway. In order to investigate the distinct structural features for the RING domains functioning as E3 ligases, several molecular dynamics simulations involving the c-Cbl, CNOT4 (with E3 ligase function), and p44 (no E3 ligase function) RING domains were conducted in this study. Our results reveal that the structural stability of the recognition site is a basic requirement for the RING domains functioning as E3 ligases. The structural stability of the recognition site is maintained by the hydrophobic core and hydrogen bonding network. Another important structural feature of the RING domains functioning as E3 ligases is the stable distances between the recognition site and the zinc ion binding sites S1 and S2. Moreover, the RING domains functioning as E3 ligases seem to exhibit lower β stability due to the higher proportion of proline residues in their sequences. However, no significant difference of the other secondary (α and turn) and the tertiary structural stabilities can be observed among these three RING domains.

KW - c-Cbl

KW - CNOT4

KW - Molecular dynamics simulations

KW - p44

KW - Proteasome

KW - Recognition site

KW - RING domain

KW - Ubiquitinylation

UR - http://www.scopus.com/inward/record.url?scp=47849114874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47849114874&partnerID=8YFLogxK

M3 - Article

C2 - 18533727

AN - SCOPUS:47849114874

VL - 26

SP - 65

EP - 73

JO - Journal of Biomolecular Structure and Dynamics

JF - Journal of Biomolecular Structure and Dynamics

SN - 0739-1102

IS - 1

ER -