6WX7

SOX2 bound to Importin-alpha 2

6WX7 の概要

• エントリーDOI: 10.2210/pdb6wx7/pdb
• 分子名称: Importin subunit alpha-1, Transcription factor SOX-2 (3 entities in total)
• 機能のキーワード: nuclear protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66313.50

構造登録者

Bikshapathi, J.,Stewart, M.,Forwood, J.K.,Aragao, D.,Roman, N. (登録日: 2020-05-09, 公開日: 2020-10-28, 最終更新日: 2023-10-25)

主引用文献

Jagga, B.,Edwards, M.,Pagin, M.,Wagstaff, K.M.,Aragao, D.,Roman, N.,Nanson, J.D.,Raidal, S.R.,Dominado, N.,Stewart, M.,Jans, D.A.,Hime, G.R.,Nicolis, S.K.,Basler, C.F.,Forwood, J.K.
Structural basis for nuclear import selectivity of pioneer transcription factor SOX2.
Nat Commun, 12:28-28, 2021

PubMed Abstract: SOX (SRY-related HMG-box) transcription factors perform critical functions in development and cell differentiation. These roles depend on precise nuclear trafficking, with mutations in the nuclear targeting regions causing developmental diseases and a range of cancers. SOX protein nuclear localization is proposed to be mediated by two nuclear localization signals (NLSs) positioned within the extremities of the DNA-binding HMG-box domain and, although mutations within either cause disease, the mechanistic basis has remained unclear. Unexpectedly, we find here that these two distantly positioned NLSs of SOX2 contribute to a contiguous interface spanning 9 of the 10 ARM domains on the nuclear import adapter IMPα3. We identify key binding determinants and show this interface is critical for neural stem cell maintenance and for Drosophila development. Moreover, we identify a structural basis for the preference of SOX2 binding to IMPα3. In addition to defining the structural basis for SOX protein localization, these results provide a platform for understanding how mutations and post-translational modifications within these regions may modulate nuclear localization and result in clinical disease, and also how other proteins containing multiple NLSs may bind IMPα through an extended recognition interface.

PubMed: 33397924
DOI: 10.1038/s41467-020-20194-0

実験手法

X-RAY DIFFRACTION (2.7 Å)