IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Average Conformations Determined from PRE Data Provide High-Resolution Maps of Transient Tertiary Interactions in Disordered Proteins
Autor/es:
JORDI SILVESTRE-RYAN; CARLOS W. BERTONCINI; ROBERT BRYN FENWICK; SANTIAGO ESTEBAN-MARTIN; XAVIER SALVATELLA
Revista:
BIOPHYSICAL JOURNAL
Editorial:
CELL PRESS
Referencias:
Lugar: United States; Año: 2013 vol. 104 p. 1740 - 1751
ISSN:
0006-3495
Resumen:
In the last decade it has become evident that disordered states of
proteins play important physiological and pathological roles and that
the transient tertiary interactions often present in these systems can
play a role in their biological activity. The structural
characterization of such states has so far largely relied on ensemble
representations, which in principle account for both their local and
global structural features. However, these approaches are inherently of
low resolution due to the large number of degrees of freedom of
conformational ensembles and to the sparse nature of the experimental
data used to determine them. Here, we overcome these limitations by
showing that tertiary interactions in disordered states can be mapped at
high resolution by fitting paramagnetic relaxation enhancement data to a
small number of conformations, which can be as low as one. This result
opens up the possibility of determining the topology of cooperatively
collapsed and hidden folded states when these are present in the vast
conformational landscape accessible to disordered states of proteins. As
a first application, we study the long-range tertiary interactions of
acid-unfolded apomyoglobin from experimentally measured paramagnetic
relaxation enhancement data.