My Interest:

My interest is in the molecular basis of the initial recognition event of protein import/export  and how the carrier/cargo protein complexes are "targeted" to the NPC (how do the cargo/carrier complexes get from the cytoplasm/nucleoplasm to the nuclear pore complex) in order for the initial recognition event to occur.

Here are some more specific questions::

-how does the protein/carrier complex actually get to the nuclear pore complex? Is it just diffusion or is their transport to the NPC mediated somehow?  How "efficient" is the nuclear transport process--for a certain amount of protein produced in the cytoplasm that is destined for the nucleus, how much actually gets to the nucleus?  Does it depend on the protein?  does it matter where in the cytoplasm the protein is produced?  How fast does the translocation from where the protein is made to the NPC occur?  What is the amount of importins produced within the cell?  When does the association of the cargo/carrier occur?  Do all these processes depend on the type of carrier protein involved?  

 What is the initial recognition event—what binds to the NPC first?  What sequences are involved in the recognition event—carrier, cargo, NPC.

How does the protein get translocated into the nuclear pore upon binding

what features of the NPC are important for excluding proteins from this initial binding event?

or when does the selection occur, maybe it is not the initial binding that excludes the proteins not destined for import

at what point is the process irreversible, when does a protein get committed for import into the nucleus

is the carrier protein required for the initial binding event? when does the carrier protein bind the cargo, far away from the pore in the cytoplasm or are there a bunch of the carrier proteins located near the pore complex?  if so how do the complexes get to the nuclear pore complex—just by diffusion or are they assisted somehow

what conformational changes take place in the nuclear pore complex as protein complexes pass through

what allows the pore complex to exclude some proteins but not others—the forces/interactions must be very weak because of the high rate of transport, what is the difference, is the initial binding/recognition event involved?

 

Project Proposal

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