5MVF

Active structure of EHD4 complexed with ADP

5MVF の概要

• エントリーDOI: 10.2210/pdb5mvf/pdb
• 関連するPDBエントリー: 5MTV
• 分子名称: EH domain-containing protein 4, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: dynamin-like, auto-inhibition, activation, endocytosis
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Early endosome membrane ; Peripheral membrane protein ; Cytoplasmic side : Q9EQP2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 59939.58

構造登録者

Melo, A.A.,Daumke, O. (登録日: 2017-01-16, 公開日: 2017-03-08, 最終更新日: 2024-01-17)

主引用文献

Melo, A.A.,Hegde, B.G.,Shah, C.,Larsson, E.,Isas, J.M.,Kunz, S.,Lundmark, R.,Langen, R.,Daumke, O.
Structural insights into the activation mechanism of dynamin-like EHD ATPases.
Proc. Natl. Acad. Sci. U.S.A., 114:5629-5634, 2017

PubMed Abstract: Eps15 (epidermal growth factor receptor pathway substrate 15)-homology domain containing proteins (EHDs) comprise a family of dynamin-related mechano-chemical ATPases involved in cellular membrane trafficking. Previous studies have revealed the structure of the EHD2 dimer, but the molecular mechanisms of membrane recruitment and assembly have remained obscure. Here, we determined the crystal structure of an amino-terminally truncated EHD4 dimer. Compared with the EHD2 structure, the helical domains are 50° rotated relative to the GTPase domain. Using electron paramagnetic spin resonance (EPR), we show that this rotation aligns the two membrane-binding regions in the helical domain toward the lipid bilayer, allowing membrane interaction. A loop rearrangement in GTPase domain creates a new interface for oligomer formation. Our results suggest that the EHD4 structure represents the active EHD conformation, whereas the EHD2 structure is autoinhibited, and reveal a complex series of domain rearrangements accompanying activation. A comparison with other peripheral membrane proteins elucidates common and specific features of this activation mechanism.

PubMed: 28228524
DOI: 10.1073/pnas.1614075114

実験手法

X-RAY DIFFRACTION (3.268 Å)