7CSO

Structure of Ephexin4 DH-PH-SH3

7CSO の概要

• エントリーDOI: 10.2210/pdb7cso/pdb
• 分子名称: Rho guanine nucleotide exchange factor 16, SULFATE ION (3 entities in total)
• 機能のキーワード: ephexin4, gef, autoinhibition, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 211511.43

構造登録者

Zhang, M.,Lin, L.,Wang, C.,Zhu, J. (登録日: 2020-08-15, 公開日: 2021-02-24, 最終更新日: 2024-03-27)

主引用文献

Zhang, M.,Lin, L.,Wang, C.,Zhu, J.
Double inhibition and activation mechanisms of Ephexin family RhoGEFs.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Ephexin family guanine nucleotide exchange factors (GEFs) transfer signals from Eph tyrosine kinase receptors to Rho GTPases, which play critical roles in diverse cellular processes, as well as cancers and brain disorders. Here, we elucidate the molecular basis underlying inhibition and activation of Ephexin family RhoGEFs. The crystal structures of partially and fully autoinhibited Ephexin4 reveal that the complete autoinhibition requires both N- and C-terminal inhibitory modes, which can operate independently to impede Ras homolog family member G (RhoG) access. This double inhibition mechanism is commonly employed by other Ephexins and SGEF, another RhoGEF for RhoG. Structural, enzymatic, and cell biological analyses show that phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4. Our study provides a mechanistic framework for understanding the fine-tuning regulation of Ephexin4 GEF activity and offers possible clues for its pathological dysfunction.

PubMed: 33597305
DOI: 10.1073/pnas.2024465118

実験手法

X-RAY DIFFRACTION (2.39 Å)