5TBK

Crystal structure of human importin a3 bound to RCC1

Summary for 5TBK

• Entry DOI: 10.2210/pdb5tbk/pdb
• Related: 4PVZ 5T94
• Descriptor: Importin subunit alpha-3, Regulator of chromosome condensation (2 entities in total)
• Functional Keywords: nuclear import, importin alpha, rcc1 like domain (rld), nls, protein transport - nuclear protein complex, protein transport / nuclear protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 16
• Total formula weight: 823730.69

Authors

Sankhala, R.S.,Lokareddy, R.K.,Pumroy, R.A.,Cingolani, G. (deposition date: 2016-09-12, release date: 2017-09-13, Last modification date: 2023-10-04)

Primary citation

Sankhala, R.S.,Lokareddy, R.K.,Begum, S.,Pumroy, R.A.,Gillilan, R.E.,Cingolani, G.
Three-dimensional context rather than NLS amino acid sequence determines importin alpha subtype specificity for RCC1.
Nat Commun, 8:979-979, 2017

PubMed Abstract: Active nuclear import of Ran exchange factor RCC1 is mediated by importin α3. This pathway is essential to generate a gradient of RanGTP on chromatin that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Here we identify the mechanisms of importin α3 selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude higher affinity than the generic importin α1, although the two isoforms share an identical NLS-binding groove. Importin α3 uses its greater conformational flexibility to wedge the RCC1 β-propeller flanking the NLS against its lateral surface, preventing steric clashes with its Armadillo-core. Removing the β-propeller, or inserting a linker between NLS and β-propeller, disrupts specificity for importin α3, demonstrating the structural context rather than NLS sequence determines selectivity for isoform 3. We propose importin α3 evolved to recognize topologically complex NLSs that lie next to bulky domains or are masked by quaternary structures.Importin α3 facilitates the nuclear transport of the Ran guanine nucleotide exchange factor RCC1. Here the authors reveal the molecular basis for the selectivity of RCC1 for importin α3 vs the generic importin α1 and discuss the evolution of importin α isoforms.

PubMed: 29042532
DOI: 10.1038/s41467-017-01057-7

Experimental method

X-RAY DIFFRACTION (3.45 Å)