Download Nuclear Pores Come into Sharper Focus Nuclear Pores Come into

THE
NUCLEAR PORE
Nuclear pore complexes (NPCs) are huge molecular
structures that penetrate the nucleus’s two lipid bilayer
membranes and mediate the transport of macromolecules
into and out of the cell’s command center. The structure
of the NPC, which consists of more than 1,000 individual
protein subunits, is coming into sharper focus, and
biologists now have a better understanding of the
function of this massive molecular machine.
Cytoplasmic
filaments
100 nm
Symmetric
core
Outer
membrane
FG repeats
Nuclear
envelope
Inner
membrane
STRUCTURE
The human NPC is composed of approximately 34 nucleoporin
proteins. The interior, or “symmetric,” core is composed of an inner
ring, and two outer rings that sit on either side of the nuclear envelope.
The NPC symmetric core helps to stabilize the extreme curvature of the
nuclear membranes abutting the pore, forms the diffusion barrier, and
provides a central transport channel. On the outside, the NPC symmetric
core is decorated with proteins called cytoplasmic filaments that participate
in protein transport and mRNA export; on the inside, the symmetric core is
associated with nuclear basket nucleoporins, which interact with chromatin and the
transcription machinery. In the central transport channel, a diffusion barrier is composed
of extensive amino-acid regions found in about a third of the nucleoporins called
phenylalanine-glycine (FG) repeats, which are intrinsically disordered and self-assemble
into a mesh-like network that prevents passive diffusion of macromolecules.
Diffusion
barrier
Nuclear
basket
FUNCTION
MACROMOLECULE TRANSPORT
Macromolecule
mRNA EXPORT
Import
Export
Nxt1
Karyopherin
RanGDP
FG
repeat
RanGTP
Nxf1
ATPase
RanGAP
Released
cargo
Nxt1
© SCOTT LEIGHTON
Macromolecule
Macromolecules—including proteins, tRNAs, and even fully assembled pre-ribosomal
subunits—are transported through the NPC in their native states with the help of proteins
called karyopherins that bind to both target molecules and to FG repeats. Upon entering the
nucleus, incoming karyopherins release their cargo when they are bound by RanGTP, the
GTP-bound conformation of a small GTPase protein called Ran. For cargoes leaving the nucleus,
RanGTP is often incorporated into karyopherin transport complexes inside the nucleus, but
encounters the Ran-activating protein RanGAP after exiting. RanGAP triggers Ran to hydrolyze
GTP into GDP, causing a conformational change and the release of the cargo into the cytoplasm.
mRNA
Nxf1
mRNP
Messenger RNAs (mRNAs) transcribed in the nucleus
are loaded with diverse proteins to form messenger
ribonucleoproteins (mRNPs) that are exported through
the NPC. These proteins include Nxf1 and Nxt1, which
bind to FG repeats in the central channel. Nucleoporins
on the cytoplasmic side of the pore recruit and activate
an ATPase to remove Nxf1/Nxt1, freeing the mRNA to be
translated by the ribosome.