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Structural insights into the activation mechanism of dynamin-like EHD ATPases
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2017 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 22, 5629-5634 p.Article in journal (Refereed) Published
Abstract [en]

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 degrees 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.

Place, publisher, year, edition, pages
2017. Vol. 114, no 22, 5629-5634 p.
Keyword [en]
dynamin superfamily, endocytic pathways, protein structure, membrane remodeling, autoinhibition
National Category
Structural Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:umu:diva-136325DOI: 10.1073/pnas.1614075114ISI: 000402296700043PubMedID: 28228524OAI: oai:DiVA.org:umu-136325DiVA: diva2:1114915
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2017-06-26Bibliographically approved

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Larsson, ElinLundmark, Richard
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Department of Medical Biochemistry and BiophysicsDepartment of Integrative Medical Biology (IMB)
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Structural BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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CiteExportLink to record
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Cite
Citation style
  • apa
  • ieee
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