Molecular dynamics simulation of the C-terminal sterile α-motif domain of human p73α: Evidence of a dynamical relationship between helices 3 and 5

Mattia Falconi, Gerry Melino, Alessandro Desideri

Research output: Contribution to journalArticle

Abstract

We used molecular dynamics simulation to evaluate the association properties of C-terminal sterile α-motif (SAM) domain of human p73α. To test the dimerization propensity of this structure we carried out four simulations: EphB2 X-ray dimer, p73 modeled dimer, p73 NMR monomer, and p73 modeled monomer with an elongated helix 5. The results show a direct interaction between helix 5 and helix 3 since a conformational collapse of helix 3 is observed when dimer contact and/or an elongation of helix 5 is introduced by modeling in p73 SAM domain. On the basis of these results we suggest that the recognition properties of the SAM domains may be modulated by the conformational state of helix 5.

Original languageEnglish
Pages (from-to)1037-1042
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume316
Issue number4
DOIs
Publication statusPublished - Apr 16 2004

Fingerprint

Molecular Dynamics Simulation
Dimers
Molecular dynamics
Computer simulation
Monomers
Dimerization
Elongation
Nuclear magnetic resonance
X-Rays
Association reactions
X rays
Sterile Alpha Motif

Keywords

  • Apoptosis
  • EphB2 dimer
  • Molecular dynamics
  • p73
  • Protein association
  • Structure destabilization
  • Tumor suppressor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "Molecular dynamics simulation of the C-terminal sterile α-motif domain of human p73α: Evidence of a dynamical relationship between helices 3 and 5",
abstract = "We used molecular dynamics simulation to evaluate the association properties of C-terminal sterile α-motif (SAM) domain of human p73α. To test the dimerization propensity of this structure we carried out four simulations: EphB2 X-ray dimer, p73 modeled dimer, p73 NMR monomer, and p73 modeled monomer with an elongated helix 5. The results show a direct interaction between helix 5 and helix 3 since a conformational collapse of helix 3 is observed when dimer contact and/or an elongation of helix 5 is introduced by modeling in p73 SAM domain. On the basis of these results we suggest that the recognition properties of the SAM domains may be modulated by the conformational state of helix 5.",
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T1 - Molecular dynamics simulation of the C-terminal sterile α-motif domain of human p73α

T2 - Evidence of a dynamical relationship between helices 3 and 5

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AU - Melino, Gerry

AU - Desideri, Alessandro

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AB - We used molecular dynamics simulation to evaluate the association properties of C-terminal sterile α-motif (SAM) domain of human p73α. To test the dimerization propensity of this structure we carried out four simulations: EphB2 X-ray dimer, p73 modeled dimer, p73 NMR monomer, and p73 modeled monomer with an elongated helix 5. The results show a direct interaction between helix 5 and helix 3 since a conformational collapse of helix 3 is observed when dimer contact and/or an elongation of helix 5 is introduced by modeling in p73 SAM domain. On the basis of these results we suggest that the recognition properties of the SAM domains may be modulated by the conformational state of helix 5.

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