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EHD2 restrains dynamics of caveolae by an ATP-dependent, membrane-bound, open conformation
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
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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, E4360-E4369 p.Article in journal (Refereed) Published
Abstract [en]

The EH-domain-containing protein 2 (EHD2) is a dynamin-related ATPase that confines caveolae to the cell surface by restricting the scission and subsequent endocytosis of these membrane pits. For this, EHD2 is thought to first bind to the membrane, then to oligomerize, and finally to detach, in a stringently regulated mechanistic cycle. It is still unclear how ATP is used in this process and whether membrane binding is coupled to conformational changes in the protein. Here, we show that the regulatory N-terminal residues and the EH domain keep the EHD2 dimer in an autoinhibited conformation in solution. By significantly advancing the use of infrared reflection-absorption spectroscopy, we demonstrate that EHD2 adopts an open conformation by tilting the helical domains upon membrane binding. We show that ATP binding enables partial insertion of EHD2 into the membrane, where G-domain-mediated oligomerization occurs. ATP hydrolysis is related to detachment of EHD2 from the membrane. Finally, we demonstrate that the regulation of EHD2 oligomerization in a membrane-bound state is crucial to restrict caveolae dynamics in cells.

Place, publisher, year, edition, pages
2017. Vol. 114, no 22, E4360-E4369 p.
Keyword [en]
EHD2, caveolae, membrane-reshaping protein, membrane-bound protein structure, infrared flection-absorption spectroscopy
National Category
Biophysics
Identifiers
URN: urn:nbn:se:umu:diva-136326DOI: 10.1073/pnas.1614066114ISI: 000402296700009PubMedID: 28223496OAI: oai:DiVA.org:umu-136326DiVA: diva2:1114014
Available from: 2017-06-22 Created: 2017-06-22 Last updated: 2017-06-22Bibliographically approved

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Mohan, JaganLarsson, ElinBlomberg, JeanetteKahra, DanaLundmark, Richard
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Department of Integrative Medical Biology (IMB)Molecular Infection Medicine Sweden (MIMS)
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CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
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  • Other locale
More languages
Output format
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