CBG 34- 4 transport models explaining different FG interactions

Question 1

what are the 4 models?

Answer 1

selective phase method/hydrogel model
forest model
virtual gate model
reduction of dimensionality model

Question 2

what do all the models have in common?

Answer 2

all agree receptors interact with nucleoporins and FG repeats.

Question 3

How do the models differ?

Answer 3

explain Fg and nucleoprin interactions in different ways

Question 4

Virtual gate model (virtual gate and polymer brush are related)

Answer 4

DEPENDS ON THERMODYNAMICS
AS CARGO MOVES THROUGH CHANNEL IT LOOSES ENTROPY (FG filaments act as brush bristles to move back + forth to hinder support)

The early ‘virtual gate’
model did not include distinct roles
for cohesive and non-cohesive FG
domains. FG domains were proposed
to act as flexible filaments that
occupy the entrances on either face of
the NPC. By repelling large
non-cargo macromolecules, these FG
filaments create an entropic barrier to
entry (Figure 1B). NTRs overcome the
entropic energy barrier by binding to
the FG domains, enabling the
passage of receptor/cargo complexes.

Related “polymer brush model” postulates that certain FG domains collapse upon receptor binding, clearing the way for receptor/cargo passage

Question 5

Forest model

Answer 5

• collapsed and extended coils(shrubs and trees)
• this makes cargo slow down due to specificity

the ‘forest’ model combines several elements of the others in a novel arrangement of FG domains: cohesive FG domains occupy the central NPC channel, as in the selective phase/hydrogel model, while non-cohesive FG domains form an entropic barrier in a concentric outer channel.

Question 6

what are FG repeat Nups

Answer 6

FG-repeat Nuclearporins. These contain unstructured repeat domains 4 and 5, with multiple FG (phenylalanine-glycine) motifs separated by loosely conserved spacers.

Question 7

what two types of fg domains are there?

Answer 7

FG domains fall into two classes: those that are cohesive and thus can participate in intermolecular interactions among themselves, and those that are non-cohesive and cannot.

Question 8

Selective phase/hydrogel model

Answer 8

suggested a decade ago

• suggests meshwork of FG repeats and size of mesh determined by clusters withing FG nulceoporins
• nuclear transport receptors bind hydrophobic clusters of FG rich repeats and hence compete with inter-repeat contacts.

In this model cohesive FG domains associate in the center of the NPC to form a sieve-like gel which acts as a barrier to free diffusion of large, but not small, non-cargo molecules . Transport receptors bind to the FG motifs in the cohesive domain, leading to transient local disruption of the gel. This allows the receptors to move through the gel without disrupting the overall barrier. In this model, no specific role is proposed for the non-cohesive FG Nups

Question 9

Reduction of dimensionality model

Answer 9

least convincing
all collapsed
default saturated with receptors then displacement (passive diffusion of small molecules through central channel)
cargo goes through random walk along walls of chanel displacing cargo free nuclear transport receptors

A ‘reduction of dimensionality’ model arranges the FG motifs peripherally with the spacers occupying the center of the pore and forming the barrier to large non-cargo molecules. Transport receptors in this model undergo a 2D random walk along the peripheral channel of FG repeats

Question 10

evidence for hydrogel model

Answer 10

in 2012 the could reproduce permeability barrier in vitro

also support from FG transport computer simulation model

Question 11

evidence forest model

Answer 11

observations of collapsed and extended FG nups

Question 12

evidence for virtual gate model

Answer 12

based on microscopy studies,looks for structures and scans

also supported by FG transport computer simulation model