INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
All-atom folding and binding of an Instrinsically Disordered Protein
Autor/es:
ITHURALDE, RE; ROITBERG, AE; TURJANSKI, AG
Reunión:
Congreso; Congreso Sociedad Argentina de BiofĂ­sica; 2014
Resumen:
Intrinsically Disordered Proteins(IDPs) lack a definite secondary structure in solution and sample many different configurations. IDPs may acquire some structure when bound to their partners, and thus the binding process needs the folding of the protein, that could follow a conformational selection process, an induced fit one or a combination of both. c-Myb is a transcription factor involved in the regulation of hemapoietic cells life cycle. TAD region of c-Myb is intrinsically disordered (30% of helicity in solution) and folds upon binding to the KIX domain[1]. The NMR structure of the complex has been solved[4] Kinetic studies of cMyb-KIX binding are consistent with a two-state process and theassociation process has an apparent activation energy of 11 kcal/mol [1,2].. A Φ value analysis was performed and proposed an ordered transition state, in contradiction with studies that show that prefolding c-Myb does not rise kon [2,3] We carried out an all atom biased MD and Go-Type coarse grain simulations. Our results show that c-Myb folds vey fast upon binding to KIX, but that pre-folded configurations of c-Myb can also bind with similar activation barrier. The transition state has a broad configuration, with helicity going from 30% to 70%. Both all atom and Go-Type simulations show similar results, indicating folding upon binding follows a native contact mechanism. To the best of our knowledge this is the first work to provide an atomistic understanding of the free energy surface of the binding process of IDPs.