5GXW

Importin and NuMA complex

Summary for 5GXW

• Entry DOI: 10.2210/pdb5gxw/pdb
• Descriptor: Importin subunit alpha-1, Peptide from Nuclear mitotic apparatus protein 1 (3 entities in total)
• Functional Keywords: importin numa complex, protein binding
• Biological source: Mus musculus (Mouse); More
• Cellular location: Cytoplasm : P52293; Nucleus . Isoform 3: Cytoplasm, cytosol . Isoform 4: Cytoplasm, cytosol : Q14980
• Total number of polymer chains: 2
• Total formula weight: 49446.52

Authors

Chang, C.-C.,Huang, T.-L.,Hsia, K.-C. (deposition date: 2016-09-20, release date: 2017-10-04, Last modification date: 2024-03-20)

Primary citation

Chang, C.-C.,Huang, T.-L.,Shimamoto, Y.,Tsai, S.-Y.,Hsia, K.-C.
Regulation of mitotic spindle assembly factor NuMA by Importin-beta
J. Cell Biol., 216:3453-3462, 2017

PubMed Abstract: Ran-guanosine triphosphatase orchestrates mitotic spindle assembly by modulation of the interaction between Importin-α/-β and spindle assembly factors (SAFs). The inhibition of SAFs performed by importins needs to be done without much sequestration from abundant nuclear localization signal (NLS) -containing proteins. However, the molecular mechanisms that determine NLS-binding selectivity and that inhibit activity of Importin-β-regulated SAFs (e.g., nuclear mitotic apparatus protein [NuMA]) remain undefined. Here, we present a crystal structure of the Importin-α-NuMA C terminus complex showing a novel binding pattern that accounts for selective NLS recognition. We demonstrate that, in the presence of Importin-α, Importin-β inhibits the microtubule-binding function of NuMA. Further, we have identified a high-affinity microtubule-binding region that lies carboxyl-terminal to the NLS, which is sterically masked by Importin-β on being bound by Importin-α. Our study provides mechanistic evidence of how Importin-α/-β regulates the NuMA functioning required for assembly of higher-order microtubule structures, further illuminating how Ran-governed transport factors regulate diverse SAFs and accommodate various cell demands.

PubMed: 28939615
DOI: 10.1083/jcb.201705168

Experimental method

X-RAY DIFFRACTION (2.394 Å)