Docking a flexible basket onto the core of the nuclear pore complex

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The nuclear basket is a structure associated with the nuclear pore complex (NPC).
• It plays a role in coupling transcription with mRNA quality control and export.
• Its precise attachment mechanism to the NPC core was previously unknown.

Purpose of the Study:

• To elucidate the molecular mechanism by which the nuclear basket docks onto the nuclear pore complex.
• To understand how this interaction influences NPC structure and function.

Main Methods:

• AlphaFold-based interaction screens
• Electron microscopy
• Membrane-templated reconstitution
• In vivo validation of protein interfaces

Main Results:

• A membrane-anchored tripartite junction was identified between the basket and NPC core.
• The Nup60 subunit of the basket utilizes short linear motifs to connect with Mlp1 and the Y-complex (Nup85).
• The reconstituted Y-complex•Nup60•Mlp1 assembly was validated in vitro and in vivo.

Conclusions:

• Short linear motif-based protein junctions can significantly alter NPC structure and function.
• This finding advances the understanding of NPC compositional and conformational heterogeneity.
• The study reveals a novel mechanism for basket-NPC core interaction.