INVESTIGADORES
FERREIRO Diego Ulises
artículos
Título:
The energy landscapes of repeat-containing proteins: topology, cooperativity, and the folding funnels of one-dimensional architectures.
Autor/es:
FERREIRO DU, WALCZAK AM, KOMIVES EA, WOLYNES PG.
Revista:
PLoS computational biology
Referencias:
Año: 2008 vol. 4 p. 1000070 - 1000070
ISSN:
1553-7358
Resumen:
Repeat-proteins are made up of near repetitions of
20- to 40-amino acid stretches. These polypeptides usually fold up into
non-globular, elongated architectures that are stabilized by the
interactions within each repeat and those between adjacent repeats, but
that lack contacts between residues distant in sequence. The inherent
symmetries both in primary sequence and three-dimensional structure are
reflected in a folding landscape that may be analyzed as a
quasi-one-dimensional problem. We present a general description of
repeat-protein energy landscapes based on a formal Ising-like treatment
of the elementary interaction energetics in and between foldons, whose
collective ensemble are treated as spin variables. The overall folding
properties of a complete "domain" (the stability and cooperativity of
the repeating array) can be derived from this microscopic description.
The one-dimensional nature of the model implies there are simple
relations for the experimental observables: folding free-energy
(DeltaG(water)) and the cooperativity of denaturation (m-value), which
do not ordinarily apply for globular proteins. We show how the
parameters for the "coarse-grained" description in terms of foldon spin
variables can be extracted from more detailed folding simulations on
perfectly funneled landscapes. To illustrate the ideas, we present a
case-study of a family of tetratricopeptide (TPR) repeat proteins and
quantitatively relate the results to the experimentally observed
folding transitions. Based on the dramatic effect that single point
mutations exert on the experimentally observed folding behavior, we
speculate that natural repeat proteins are "poised" at particular
ratios of inter- and intra-element interaction energetics that allow
them to readily undergo structural transitions in physiologically
relevant conditions, which may be intrinsically related to their
biological functions.