5T94

Crystal structure of Kap60 bound to yeast RCC1 (Prp20)

5T94 の概要

• エントリーDOI: 10.2210/pdb5t94/pdb
• 関連するPDBエントリー: 4PVZ
• 分子名称: Guanine nucleotide exchange factor SRM1, Importin subunit alpha (3 entities in total)
• 機能のキーワード: nuclear import, importin alpha, rcc1 like domain, rld, nls, protein transport - nuclear protein complex, protein transport / nuclear protein
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 113581.73

構造登録者

Sankhala, R.S.,Lokareddy, R.K.,Pumroy, R.A.,Cingolani, G. (登録日: 2016-09-09, 公開日: 2017-09-13, 最終更新日: 2023-10-04)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.631 Å)