puc-header

Membrane Deformation Ability of the Ankyrin Repeat and KH Domain-Containing Protein 1 (ANKHD1) and Its Involvement in the Early Endosome Enlargement

41 Pages Posted: 10 Nov 2018 Sneak Peek Status: Published

See all articles by Manabu Kitamata

Manabu Kitamata

Nara Institute of Science and Technology - Division of Biological Science

Kyoko Hanawa-Suetsugu

Nara Institute of Science and Technology - Division of Biological Science

Kohei Maruyama

Nara Institute of Science and Technology

Shiro Suetsugu

Nara Institute of Science and Technology - Division of Biological Science

More...

Abstract

Ankyrin-repeat domains (ARDs) are conserved in large numbers of proteins. ARDs are composed of ankyrin repeats (ANKs). The number of repeats varies among ARDs, and the sequence of ANKs often adopt curved structures reminiscent of the Bin-Amphiphysin-Rvs (BAR) domain, which is the dimeric membrane scaffold for membrane tubulation. BAR domains sometimes have amphipathic helices that enable the membrane scission for vesicle formation. Whether ARD-containing proteins exhibit similar membrane deformation and scission had been unclear. We found that the ARD of ankyrin repeat and KH domain-containing protein 1 (ANKHD1) dimerize and efficiently deform membranes into tubules and vesicles. ANKHD1 contains 25 ANKs that are divided into two groups; the first 15 ANKs and the latter 10 ANKs. We found that the first 15 ANKs can form a dimer, and the latter 10 ANKs enable membrane tubulation and vesiculation. These 10 ANKs were shown to have an adjacent amphipathic helix and were predicted to have a curved structure with a positively charged surface, analogous to BAR domains. Mutations of the positively charged amino acid residues and the deletion of the amphipathic helix abolished the membrane vesiculation ability. Interestingly, the dimeric 25 ANKs displayed significantly higher vesiculation ability than the 10 ANKs. Knockdown and localization of ANKHD1 suggested its involvement in the negative regulation of the enlargement of early endosomes. These results indicate that ANKHD1 causes vesiculation of the early endosomal membrane in a manner that is similar to the BAR domain protein.

Keywords: ankyrin repeat domain, BAR domain, membrane deformation, membrane vesiculation, early endosome

Suggested Citation

Kitamata, Manabu and Hanawa-Suetsugu, Kyoko and Maruyama, Kohei and Suetsugu, Shiro, Membrane Deformation Ability of the Ankyrin Repeat and KH Domain-Containing Protein 1 (ANKHD1) and Its Involvement in the Early Endosome Enlargement (November 9, 2018). Available at SSRN: https://ssrn.com/abstract=3281657 or http://dx.doi.org/10.2139/ssrn.3281657
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Manabu Kitamata

Nara Institute of Science and Technology - Division of Biological Science

Japan

Kyoko Hanawa-Suetsugu

Nara Institute of Science and Technology - Division of Biological Science

Japan

Kohei Maruyama

Nara Institute of Science and Technology

5 Takayamacho
Ikoma, 630-0192
Japan

Shiro Suetsugu (Contact Author)

Nara Institute of Science and Technology - Division of Biological Science ( email )

Japan

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
182
Downloads
9