5MVF

Active structure of EHD4 complexed with ADP

Summary for 5MVF

• Entry DOI: 10.2210/pdb5mvf/pdb
• Related: 5MTV
• Descriptor: EH domain-containing protein 4, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: dynamin-like, auto-inhibition, activation, endocytosis
• Biological source: Mus musculus (Mouse)
• Cellular location: Early endosome membrane ; Peripheral membrane protein ; Cytoplasmic side : Q9EQP2
• Total number of polymer chains: 1
• Total formula weight: 59939.58

Authors

Melo, A.A.,Daumke, O. (deposition date: 2017-01-16, release date: 2017-03-08, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.268 Å)