Membrane-Deformation Ability of ANKHD1 Is Involved in the Early Endosome Enlargement

• Published in: iScience Vol. 17; pp. 101 - 118
• Main Authors: Kitamata, Manabu, Hanawa-Suetsugu, Kyoko, Maruyama, Kohei, Suetsugu, Shiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.07.2019; Elsevier
• Subjects: Biochemistry; Biological Sciences; Cell Biology; Membrane Architecture; Molecular Biology; Biological Sciences; Biochemistry; Membrane Architecture; Molecular Biology; Cell Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.06.020

Ankyrin-repeat domains (ARDs) are conserved in large numbers of proteins. ARDs are composed of various numbers of ankyrin repeats (ANKs). ARDs often adopt curved structures reminiscent of the Bin-Amphiphysin-Rvs (BAR) domain, which is the dimeric scaffold for membrane tubulation. BAR domains sometimes have amphipathic helices for membrane tubulation and vesiculation. However, it is unclear whether ARD-containing proteins exhibit similar membrane deformation properties. We found that the ARD of ANK and KH domain-containing protein 1 (ANKHD1) dimerize and deform membranes into tubules and vesicles. Among 25 ANKs of ANKHD1, the first 15 ANKs can form a dimer and the latter 10 ANKs enable membrane tubulation and vesiculation through an adjacent amphipathic helix and a predicted curved structure with a positively charged surface, analogous to BAR domains. Knockdown and localization of ANKHD1 suggested its involvement in the negative regulation of early endosome enlargement owing to its membrane vesiculation. [Display omitted] •ANKHD1 is a large protein of 270 kDa, containing 25 ankyrin repeats•ANKHD1 generates membrane tubules and vesicles by its ankyrin-repeat domain (ARD).•The ARD has an amphipathic helix and a predicted curved structure, like BAR domains•ANKHD1 negatively regulates early endosome enlargement by its vesiculation ability Biological Sciences; Biochemistry; Molecular Biology; Membrane Architecture; Cell Biology