Comprehensive structure and functional adaptations of the yeast nuclear pore complex.

Area of Science:

• Cell Biology
• Structural Biology
• Biochemistry

Background:

• Nuclear pore complexes (NPCs) are essential molecular machines regulating transport between the nucleus and cytoplasm.
• Understanding NPC structure is crucial for deciphering nucleocytoplasmic transport mechanisms.

Purpose of the Study:

• To elucidate the high-resolution structure of the isolated yeast NPC, focusing on the inner ring.
• To investigate the role of flexible connectors in NPC assembly and function.
• To model the in situ NPC structure and identify features related to transport regulation.

Main Methods:

• Cryo-electron microscopy (cryo-EM) at sub-nanometer resolution.
• Cryo-electron tomography (cryo-ET) for in situ structural analysis.
• Analysis of nucleoporin interactions and transport factor motifs.

Main Results:

• Resolved the inner ring of the yeast NPC, detailing flexible connectors linking structural and functional layers.
• Identified conserved interaction motifs between nucleoporins and transport factors, suggesting links between assembly and transport.
• Provided evidence for three major NPC variants with potential functional specializations.
• Developed a model of the in situ NPC, revealing features of the nuclear basket, central transporter, and the Pom152 ring's role in restricting dilation.

Conclusions:

• The structural plasticity of NPCs may be essential for efficient nucleocytoplasmic transport.
• Flexible connectors are key structural elements potentially regulated by phosphorylation and disassembly.
• Similar interaction motifs suggest evolutionary and mechanistic links between NPC assembly and transport processes.