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SUMMARY:The Molecular Mechanism of Nuclear Protein Import - Dr Murray Stew
 art\, MRC-LMB\, Cambridge
DTSTART:20090227T141500Z
DTEND:20090227T151500Z
UID:TALK16199@talks.cam.ac.uk
CONTACT:Jurij Kotar
DESCRIPTION:The nuclear import of proteins through nuclear pore complexes 
 (NPCs) illustrates how a complex biological function can be generated by a
  spatially and temporally organized cycle of interactions between cargoes\
 , carriers and the Ras family GTPase\, Ran. Recent work has given consider
 able insight into this process\, especially about how interactions are coo
 rdinated and the basis for the molecular recognition that underlies the pr
 ocess. Overall nuclear protein import can be considered in terms of three 
 steps: first\, a cargo:carrier complex is formed in the cytoplasm\; next\,
  the cargo:carrier complex is translocated through the NPC transport chann
 el\; and finally the cargo is dissociated from the carrier in the nucleus 
 and the carrier is recycled to the cytoplasm.  The assembly and disassembl
 y steps are orchestrated by the nucleotide state of the Ran GTPase.  Thus\
 , cytoplasmic RanGDP facilitates assembly of the cargo:carrier complex\, w
 hereas nuclear RanGTP  dissociates it.  The nucleotide state of Ran is det
 ermined by its GTPase activating protein (RanGAP) being located in the cyt
 oplasm while its guanine nucleotide exchange factor (RanGEF or RCC1) is nu
 clear.  Translocation of the cargo:carrier complex through the pore does n
 ot require energy and functions to equilibrate the complex between the cyt
 oplasmic and nuclear compartments\; transport is instead driven by import 
 complex dissociation in the nucleus with the energy deriving from GTP hydr
 olysis ultimately being liberated in the cytoplasm.  Overall\, nuclear pro
 tein import is an example of a process driven by rectified Brownian motion
  (a "thermal ratchet") with energy being used primarily for sorting\, gene
 rating a biological version of Maxwell's demon.  Although considerable pro
 gress has been made in identifying and characterizing the molecular intera
 ctions in the soluble phase that drive the nuclear protein import cycle\, 
 understanding the precise mechanism of translocation through NPCs and how 
 the NPC generates a barrier to other macromolecules remain major challenge
 s.\n
LOCATION:Pippard Lecture Theatre\, Cavendish Laboratory
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