[Todos] Lunes 10/12 - 13.00 hs - Seminarios DQIAQF - INQUIMAE

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Seminarios DQIAQF - INQUIMAE, Lunes 10 de diciembre - 13 hs.

Aula de Seminarios INQUIMAE - DQIAQF
Facultad de Ciencias Exactas y Naturales
Ciudad Universitaria - Pab. 2  -  Piso 3

Molecular Organization and Translocation in Nuclear Pore Complexes

Igal Szleifer

Department of Biomedical Engineering
Department of Chemistry
Department of Chemical and Biological Engineering
Department of Medicine
Chemistry of Life Processes Institute
Northwestern University

In this talk we will present the study of the molecular structure of yeast
Nuclear Pore Complex (NPC) and the translocation of model particles. The
theoretical predictions have been carried out with a molecular theory that
accounts for the geometry of the pore and the amino-acid sequence and
anchoring position of the unfolded domains of the nucleoporin proteins (the
FG-Nups), which control selective transport through the pore. The theory
explicitly models the electrostatic, hydrophobic, steric, conformational
and acid-base properties of the FG-Nups. The electrostatic potential within
the pore, which arises from the specific charge distribution of the
FG-Nups, is predicted to be negative close to pore walls and positive along
pore axis. The positive electrostatic potential facilitates the
translocation of negatively charged particles and the free energy barrier
for translocation decreases for increasing particle hydrophobicity. The
above results agree with the experimental observation that transport
receptors which form complexes with hydrophilic/neutral or positively
charged proteins to transport them through the NPC, are both hydrophobic
and strongly negatively charged. The predictions from the theory show that
the effects of electrostatic and hydrophobic interactions on the
translocating potential are cooperative and non-equivalent due to the
interaction-dependent reorganization of the FG-Nups in the presence of the
translocating particle. The combination of electrostatic and hydrophobic
interactions can give rise to complex translocation potentials displaying a
combination of wells and barriers, in contrast to the simple barrier
potential observed for a hydrophilic/neutral translocating particle. Our
predictions demonstrate the importance of explicitly considering the amino
acid sequence and hydrophobic, electrostatic and steric interactions in
understanding the translocation through the NPC.