2013-04-17
10:15 at HCI J 574

The Nuclear Pore Complex: Geometry, Hydrophobicity, Charge, Sequence

Yitzhak Rabin

Bar-Ilan University, Israel

The molecular structure of the Nuclear Pore Complex (NPC) and the translocation of model particles have been studied 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 combination of electrostatic and hydrophobic interactions gives rise to complex potential of mean force, displaying a combination of wells and barriers, in contrast to the simple barrier potential observed for a hydrophilic/neutral translocating particle. This work demonstrates the importance of explicitly considering the amino acid sequence and hydrophobic, electrostatic and steric interactions in understanding the translocation through the NPC.