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Leucine‐rich hydrophobic clusters promote folding of the N‐terminus of the intrinsically disordered transactivation domain of p53
Author(s) -
Espinoza-Fonseca L. Michel
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.12.060
Subject(s) - transactivation , intrinsically disordered proteins , molecular dynamics , biophysics , microsecond , chemistry , folding (dsp implementation) , energy landscape , leucine rich repeat , protein folding , crystallography , conformational ensembles , chemical physics , biochemistry , physics , biology , computational chemistry , transcription factor , receptor , gene , astronomy , electrical engineering , engineering
Molecular dynamics simulations have been performed on the intrinsically disordered 39‐residue N‐terminal transactivation domain of p53 (p53 1‐39 ). Simulations not only revealed that p53 1‐39 is natively compact, but also possesses a folded structure. Furthermore, leucine‐rich hydrophobic clusters were found to play a crucial role in the formation and stabilization of the folded structure of p53 1‐39 . Collapsing in the sub‐microsecond timescale might allow for rapid conformational turnovers of p53 1‐39 , necessary for its efficient transactivation activity and modulation. Fast collapsing might be the result of unique conformational landscapes, featuring several energy minima separated by small energy barriers. It is suggested that IDPs with highly specialized functions in the cell, such as transactivation, possibly display more ordered patterns than their less specialized counterparts.