Crystal structure of human nuclear pore complex component NUP43

Area of Science:

• Molecular Biology
• Structural Biology
• Cell Biology

Background:

• Nuclear pore complexes (NPCs) regulate transport between the nucleus and cytoplasm.
• The Nup107 subcomplex is essential for NPC assembly and function.
• Understanding the structure of NPC components like hNup43 is vital for elucidating nuclear transport mechanisms.

Purpose of the Study:

• To determine the crystal structure of human Nup43 (hNUP43).
• To investigate the interactions of hNUP43 with other nucleoporins, specifically hNup37 and hNup133.
• To characterize the assembly of a ternary complex involving hNup43, hNup85, and Seh1L.

Main Methods:

• X-ray crystallography was used to solve the structure of hNUP43.
• Isothermal Titration Calorimetry (ITC) was employed to assess protein-protein interactions.
• Analytical gel filtration was performed to study complex formation.

Main Results:

• The crystal structure revealed that hNup43 adopts a seven-bladed β-propeller fold.
• ITC experiments confirmed that hNup43 does not directly interact with hNup37 or hNup133.
• Analytical gel filtration demonstrated that the hNup85-Seh1L binary complex recruits hNup43 to form a ternary complex.

Conclusions:

• hNup43's structure is characterized by a β-propeller fold.
• hNup43 does not directly bind hNup37 or hNup133, suggesting its role in NPC assembly is mediated through other interactions.
• hNup43 is recruited to form a ternary complex with hNup85-Seh1L, providing insights into the modular assembly of the Nup107 subcomplex.