[Todos] MARTES Seminario en DF: Carlos Bustamante (UC Berkeley): 10hs, Aula Seminario, Pab. I

[Augusto Roncaglia]

SEMINARIO EN EL DEPARTAMENTO DE F�SICA FCEYN - UBA


                        En el Aula Seminario, 2do piso, Pabellón I,

                        Martes 13/5, 10hs:

                        CARLOS BUSTAMANTE

                        University of California, Berkeley, USA


*                        Use of Crooks Fluctuation Theorem to Study the
Interdomain Folding Cooperativity of a Protein*

Proteins are complex functional molecules that tend to segregate into
structural regions. Throughout evolution, biology has harnessed this
modularity to carry out specialized roles and regulate higher-order
functions such as allostery. Cooperative communication between protein
regions is important for catalysis, regulation, and efficient folding.
However, how domains communicate and contribute to a protein’s energetics
and folding is still poorly understood. Bulk methods rely on a simultaneous
and global perturbation of the system and can miss potential intermediates,
thereby overestimating protein cooperativity and domain coupling. To
overcome this problem we used single molecule manipulation methods (optical
tweezers or AFM) to mechanically induce the selective unfolding of
particular regions of a single protein while monitoring the response of
other regions not directly affected by the external force. We applied one
of the newly derived fluctuation theorems (Crook’s theorem) that allows to
extract equilibrium thermodynamic information from the irreversible work
done on a system. In this way we evaluate the cooperativity between domains
by determining the unfolding energy of topological variants pulled along
different directions. We show that topology of the polypeptide chain
critically determines the folding cooperativity between domains, and what
parts of the folding/unfolding landscape are explored. We speculate that
proteins may have evolved to select certain topologies that increase
coupling between regions to avoid areas of the landscape that lead to
kinetic trapping and misfolding.
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