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The yeast nuclear pore complex: composition, architecture, and transport mechanism.

Rout MP, Aitchison JD, Suprapto A, Hjertaas K, Zhao Y, Chait BT - J. Cell Biol. (2000)

Bottom Line: Therefore, we have taken a comprehensive approach to classify all components of the yeast NPC (nucleoporins).This involved identifying all the proteins present in a highly enriched NPC fraction, determining which of these proteins were nucleoporins, and localizing each nucleoporin within the NPC.Using these data, we present a map of the molecular architecture of the yeast NPC and provide evidence for a Brownian affinity gating mechanism for nucleocytoplasmic transport.

View Article: PubMed Central - PubMed

Affiliation: The Rockefeller University, New York, NY 10021, USA. rout@rockvax.rockefeller.edu

ABSTRACT
An understanding of how the nuclear pore complex (NPC) mediates nucleocytoplasmic exchange requires a comprehensive inventory of the molecular components of the NPC and a knowledge of how each component contributes to the overall structure of this large molecular translocation machine. Therefore, we have taken a comprehensive approach to classify all components of the yeast NPC (nucleoporins). This involved identifying all the proteins present in a highly enriched NPC fraction, determining which of these proteins were nucleoporins, and localizing each nucleoporin within the NPC. Using these data, we present a map of the molecular architecture of the yeast NPC and provide evidence for a Brownian affinity gating mechanism for nucleocytoplasmic transport.

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Diagram of NPC illustrating a model for nucleocytoplasmic transport. See Discussion for details.
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Figure 11: Diagram of NPC illustrating a model for nucleocytoplasmic transport. See Discussion for details.

Mentions: Consider a cargo imported by its kap into the nucleoplasm (Fig. 11). The cargo alone cannot easily pass through the diffusion barrier of the NPC. In the cytoplasm, the kap is exposed only to Ran-GDP, allowing it to acquire the cargo. This cargo–kap complex can now bind the NPC (Fig. 11 I), passing through the now effectively open Brownian gate and diffusing across the NPC by binding symmetric FG nups. This allows the cargo–kap complex access to both faces of the NPC (Fig. 11 II). We propose that in this state, the cargo–kap complex has its highest affinity for the one-sided FG nups on the nuclear face. At the nuclear face, the kap moves preferentially away from the symmetric region of the nuclear pore to these higher affinity binding sites, preventing its exchange back to the cytoplasmic face. In the absence of any other influence this high affinity interaction would be stable, and the cargo–kap complex would arrest here, bound to the FG nups at the nuclear extremity of the NPC (Fig. 11 III). This situation is seen in the case of kap mutants that cannot bind Ran (Gorlich et al. 1996). However, the peripheral localization of these nups exposes their bound kap complex to the nucleoplasmic milieu and in particular, to Ran-GTP. The binding of Ran-GTP to the kap induces cargo release and undocking from the NPC, which causes the cargo and kap to be liberated into the nucleoplasm (Fig. 11 IV). Once nucleoplasmic, the cargo can no longer bind the NPC, and the Brownian gate, in effect, shuts.


The yeast nuclear pore complex: composition, architecture, and transport mechanism.

Rout MP, Aitchison JD, Suprapto A, Hjertaas K, Zhao Y, Chait BT - J. Cell Biol. (2000)

Diagram of NPC illustrating a model for nucleocytoplasmic transport. See Discussion for details.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169373&req=5

Figure 11: Diagram of NPC illustrating a model for nucleocytoplasmic transport. See Discussion for details.
Mentions: Consider a cargo imported by its kap into the nucleoplasm (Fig. 11). The cargo alone cannot easily pass through the diffusion barrier of the NPC. In the cytoplasm, the kap is exposed only to Ran-GDP, allowing it to acquire the cargo. This cargo–kap complex can now bind the NPC (Fig. 11 I), passing through the now effectively open Brownian gate and diffusing across the NPC by binding symmetric FG nups. This allows the cargo–kap complex access to both faces of the NPC (Fig. 11 II). We propose that in this state, the cargo–kap complex has its highest affinity for the one-sided FG nups on the nuclear face. At the nuclear face, the kap moves preferentially away from the symmetric region of the nuclear pore to these higher affinity binding sites, preventing its exchange back to the cytoplasmic face. In the absence of any other influence this high affinity interaction would be stable, and the cargo–kap complex would arrest here, bound to the FG nups at the nuclear extremity of the NPC (Fig. 11 III). This situation is seen in the case of kap mutants that cannot bind Ran (Gorlich et al. 1996). However, the peripheral localization of these nups exposes their bound kap complex to the nucleoplasmic milieu and in particular, to Ran-GTP. The binding of Ran-GTP to the kap induces cargo release and undocking from the NPC, which causes the cargo and kap to be liberated into the nucleoplasm (Fig. 11 IV). Once nucleoplasmic, the cargo can no longer bind the NPC, and the Brownian gate, in effect, shuts.

Bottom Line: Therefore, we have taken a comprehensive approach to classify all components of the yeast NPC (nucleoporins).This involved identifying all the proteins present in a highly enriched NPC fraction, determining which of these proteins were nucleoporins, and localizing each nucleoporin within the NPC.Using these data, we present a map of the molecular architecture of the yeast NPC and provide evidence for a Brownian affinity gating mechanism for nucleocytoplasmic transport.

View Article: PubMed Central - PubMed

Affiliation: The Rockefeller University, New York, NY 10021, USA. rout@rockvax.rockefeller.edu

ABSTRACT
An understanding of how the nuclear pore complex (NPC) mediates nucleocytoplasmic exchange requires a comprehensive inventory of the molecular components of the NPC and a knowledge of how each component contributes to the overall structure of this large molecular translocation machine. Therefore, we have taken a comprehensive approach to classify all components of the yeast NPC (nucleoporins). This involved identifying all the proteins present in a highly enriched NPC fraction, determining which of these proteins were nucleoporins, and localizing each nucleoporin within the NPC. Using these data, we present a map of the molecular architecture of the yeast NPC and provide evidence for a Brownian affinity gating mechanism for nucleocytoplasmic transport.

Show MeSH