How proteins cross the Nuclear Pore Complex

Over this past summer I saw Dirk Görlich give a talk about how the multitude of FG repeats found within the nuclear pore complex (NPC), form a gel like matrix. This "elastic hydrogel" acts as the major barrier within the NPC. Although the gel can prevent the passage of most large molecules (>30kD), it is permeable to nuclear transport receptors (NTRs). Note that all this "story" was published in the November 3rd edition of Science Magazine (link). In that paper there's a nice diagram in the that explains it all:

i-2fe236995e55a2451bae1c2f5e0a9134-NPCdif.jpg

i-3d8f15b5d4fc8ac7858817d23cc43b65-NPC2.jpg
An "FG repeat" is a long stretch of amino acids that form non-covalent cross linking type interactions to form a gel like substance within the pore. FG repeats are found in many NPC proteins, and each of these proteins contains many of these motifs. (Shown here are the FG repeats found in Nsp1, a single NPC protein). Proteins that are too big to diffuse within the holes of the matrix are barred from crossing the gel. NTRs on the other hand can displace the FG-FG interactions by forming FG-NTR interactions and thus participating in the gel's scaffold. This property allows the NTRs (and associated proteins) to cross the matrix while maintaining the integrity of the gel scaffold (see cartoon above).

i-7705062c594e666003c8ea850e3ade36-NPC3.gif
Gorlich's lab has even been able to form this gel in the lab. They show that if enough of the FG repeats are mutated, then the interactions are broken and the gel can't "solidify" (or "gummy-fy"?). These mutations also make the NPCs more leaky in yeast.

So it turns out that the core of the NPC is like a gummy bear that can absorb like molecules and exclude everything else.

Ref:
Steffen Frey, Ralf P. Richter, Dirk Görlich
FG-Rich Repeats of Nuclear Pore Proteins Form a Three-Dimensional Meshwork with Hydrogel-Like Properties
Science (06) 314:815-817

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As much as I like this paper (I think it's one of the coolest papers this year): they only showed that import factors can get INTO the gel - but, they cannot get OUT. So the gummi bear may only be half of the story...

Yeah,

I think that they could calculate a steady-state equilibrium between NTRs the Gel phase and the non-Gel phase (aqueous? phase). As long as the equilibrium is not too skewed towards NTRs being in the gel (turning the gel into a sink for NTRs) the system may work fine.

I agree, this is one of the most insightful papers of the year.

By Acme Scientist (not verified) on 06 Dec 2006 #permalink