6K06

Crystal structure of Importin-alpha and phosphomimetic GM130

Summary for 6K06

• Entry DOI: 10.2210/pdb6k06/pdb
• Descriptor: Peptide from Golgin subfamily A member 2, Importin subunit alpha-1 (3 entities in total)
• Functional Keywords: importin alpha, gm130, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 52696.28

Authors

Chang, C.-C.,Chen, C.-J.,Pien, Y.-C.,Tsai, S.-Y.,Hsia, K.-C. (deposition date: 2019-05-05, release date: 2019-10-02, Last modification date: 2023-11-22)

Primary citation

Chang, C.-C.,Chen, C.-J.,Grauffel, C.,Pien, Y.-C.,Lim, C.,Tsai, S.-Y.,Hsia, K.-C.
Ran pathway-independent regulation of mitotic Golgi disassembly by Importin-alpha.
Nat Commun, 10:4307-4307, 2019

PubMed Abstract: To facilitate proper mitotic cell partitioning, the Golgi disassembles by suppressing vesicle fusion. However, the underlying mechanism has not been characterized previously. Here, we report a Ran pathway-independent attenuation mechanism that allows Importin-α (a nuclear transport factor) to suppress the vesicle fusion mediated by p115 (a vesicular tethering factor) and is required for mitotic Golgi disassembly. We demonstrate that Importin-α directly competes with p115 for interaction with the Golgi protein GM130. This interaction, promoted by a phosphate moiety on GM130, is independent of Importin-β and Ran. A GM130 K34A mutant, in which the Importin-α-GM130 interaction is specifically disrupted, exhibited abundant Golgi puncta during metaphase. Importantly, a mutant showing enhanced p115-GM130 interaction presented proliferative defects and G2/M arrest, demonstrating that Importin-α-GM130 binding modulates the Golgi disassembly that governs mitotic progression. Our findings illuminate that the Ran and kinase-phosphatase pathways regulate multiple aspects of mitosis coordinated by Importin-α (e.g. spindle assembly, Golgi disassembly).

PubMed: 31541088
DOI: 10.1038/s41467-019-12207-4

Experimental method

X-RAY DIFFRACTION (1.75 Å)