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More generally, at a distance of ∼30 Å from the NES-binding groove, the RanBP3 RBD is well positioned to influence the cargo selectivity of CRM1 by interacting with (or excluding) cargo moieties that occupy volumes adjacent to (or overlapping with) that occupied by the RBD on the CRM1 surface.
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The multiple Atg8 binding sites in Atg19 subsequently mediate the selective interaction with membrane localized, locally concentrated Atg8, enabling Atg19 to bend the membrane tightly around the cargo and to exclude non-cargo material from its delivery into the vacuole (Baba et al., 1997; Sawa-Makarska et al., 2014).
Similarly, imaging of cells expressing GFP-tagged procollagen shows that this particular cargo appears in vesicular-tubular transport carriers that appear to exclude other cargo proteins (Stephens and Pepperkok 2002).
These two properties enable Atg19 to bend the membrane tightly around the cargo and thereby to exclude non-cargo material from the Cvt vesicles (Baba et al., 1997; Sawa-Makarska et al., 2014).
With regards to the NPC, brush-like FG Nups could collectively give rise to a corona-like barrier that would entropically exclude nonspecific cargoes from the NPC vicinity, as was first proposed by the virtual gating model.
This need not exclude the resulting protein/lipid microdomains attracting further cargo or excluding residents based on physical properties alone.
Alternatively, COPII vesicles coated by SEC24C/D might exclude selected soluble cargos such as PCSK9.
This deficit can therefore explain the impairment in transmitter release at the presynaptic terminals without, however, excluding the possibility that the impaired transport of other cargoes is also involved.
Elegant reconstitution experiments have suggested that GTP hydrolysis by Sar1, and its regulation by cargo proteins, acts to ensure that improper cargoes are excluded from nascent buds (Sato and Nakano 2004).
The binding to SNX5 by IncE may exclude its association with cargo molecules such as CI-MPR.
Since the intra-Golgi diffusion rate of soluble cargoes is an order of magnitude faster than either entry into or exit out of the Golgi excluding them in the simulations does not affect the conclusions.
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