Molecular dynamics simulation of the C-terminal sterile alpha-motif domain of human p73alpha: evidence of a dynamical relationship between helices 3 and 5.
We used molecular dynamics simulation to evaluate the association properties of C-terminal sterile alpha-motif (SAM) domain of human p73alpha. 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.
Falconi
Mattia
M
INFM and Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
Melino
Gerry
G
Desideri
Alessandro
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019281:Dimerization; D016147:Genes, Tumor Suppressor; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D009687:Nuclear Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins