Cell Biochemistry and Biophysics

, Volume 44, Issue 3, pp 475–489 | Cite as

NMR structure of the p63 SAM domain and dynamical properties of G534V and T537P pathological mutants, identified in the AEC syndrome

  • Daniel O. Cicero
  • Mattia Falconi
  • Eleonora Candi
  • Sonia Mele
  • Bruno Cadot
  • Almerinda Di Venere
  • Stefano Rufini
  • Gerry Melino
  • Alessandro Desideri
Original Article


The p63 protein is crucial for epidermal development, and its mutations cause the extrodactyly ectodermal dysplasia and cleft lip/palate syndrome. The three-dimensional solution structure of the p63 sterile α-motif (SAM) domain (residues 505–579), a region crucial to explaining the human genetic disease ankyloblepharon-ectodermal dysplasia-clefting syndrome (AEC), has been determined by nuclear magnetic resonance spectroscopy. The structure indicates that the domain is a monomer with the characteristic five-helix bundle topology observed in other SAM domains. It includes five tightly packed helices with an extended hydrophobic core to form a globular and compact structure. The dynamics of the backbone and the global correlation time of the molecule have also been investigated and compared with the dynamical properties obtained through molecular dynamics simulation. Attempts to purify the pathological G534V and T537P mutants, originally identified in AEC, were not successful because of the occurrence of unspecific proteolytic degradation of the mutated SAM domains. Analysis of the structural dynamic properties of the G534V and T537P mutants through molecular dynamics simulation and comparison with the wild type permits detection of differences in the degree of free-dom of individual residues and discussion of the possible causes for the pathology.

Index Entries

p63 p53 family ankyloblepharon-ectodermal dysplasia-clefting syndrome ectodermal dysplasia and cleft lip/palate syndrome NMR structure molecular dynamics structure destabilization 


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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Daniel O. Cicero
    • 1
  • Mattia Falconi
    • 2
  • Eleonora Candi
    • 3
  • Sonia Mele
    • 1
  • Bruno Cadot
    • 3
  • Almerinda Di Venere
    • 3
  • Stefano Rufini
    • 2
  • Gerry Melino
    • 3
  • Alessandro Desideri
    • 2
  1. 1.Department of Science and Chemical TechnologiesUniversity of Rome “Tor Vergata”RomeItaly
  2. 2.INFM and Department of BiologyUniversity of Rome “Tor Vergata”RomeItaly
  3. 3.Biochemistry Laboratory, IDI-IRCCS,c/o Department of Experimental Medicine and Biochemical SciencesUniversity of Rome “Tor Vergata”RomeItaly

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