Solution structure of human growth arrest and DNA damage 45alpha (Gadd45alpha) and its interactions with proliferating cell nuclear antigen (PCNA) and Aurora A kinase.
Gadd45alpha is a nuclear protein encoded by a DNA damage-inducible gene. Through its interactions with other proteins, Gadd45alpha participates in the regulation of DNA repair, cell cycle, cell proliferation, and apoptosis. The NMR structure of human Gadd45alpha has been determined and shows an alpha/beta fold with two long disordered and flexible regions at the N terminus and one of the loops. Human Gadd45alpha is predominantly monomeric in solution but exists in equilibrium with dimers and other oligomers whose population increases with protein concentration. NMR analysis shows that Aurora A interacts through its N-terminal domain with a region of human Gadd45alpha encompassing the site of dimerization, suggesting that the oligomerization of Gadd45alpha could be a regulatory mechanism to modulate its interactions with Aurora A, and possibly with other proteins too. However, Gadd45alpha appears to interact only weakly with PCNA through its flexible loop, in contrast with previous and contradictory reports.
Sánchez
Ricardo
R
Structural Biology Unit, CIC bioGUNE, Parque Tecnológico de Bizkaia, Ed. 800, Derio E-48160, Spain.
Pantoja-Uceda
David
D
Prieto
Jesús
J
Diercks
Tammo
T
Marcaida
María J
MJ
Montoya
Guillermo
G
Campos-Olivas
Ramón
R
Blanco
Francisco J
FJ
D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017433:Protein Structure, Secondary; D012996:Solutions; D000097642:GADD45 Proteins
D064096:Aurora Kinase A; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D017346:Protein Serine-Threonine Kinases; D012996:Solutions; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C576918:Aurka protein, mouse
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