title: A PH domain in ACAP1 possesses key features of the BAR domain in promoting membrane curvature.
abstract: The BAR (Bin-Amphiphysin-Rvs) domain undergoes dimerization to produce a curved protein structure, which superimposes onto membrane through electrostatic interactions to sense and impart membrane curvature. In some cases, a BAR domain also possesses an amphipathic helix that inserts into the membrane to induce curvature. ACAP1 (Arfgap with Coil coil, Ankyrin repeat, and PH domain protein 1) contains a BAR domain. Here, we show that this BAR domain can neither bind membrane nor impart curvature, but instead requires a neighboring PH (Pleckstrin Homology) domain to achieve these functions. Specific residues within the PH domain are responsible for both membrane binding and curvature generation. The BAR domain adjacent to the PH domain instead interacts with the BAR domains of neighboring ACAP1 proteins to enable clustering at the membrane. Thus, we have uncovered the molecular basis for an unexpected and unconventional collaboration between PH and BAR domains in membrane bending.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Hong Kong 999077, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fan
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Bingquan
authors.initials: B
authors.lastname: Gao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Deng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qiangjun
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Egelman
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: vhsu@research.bwh.harvard.edu.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Hsu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: feisun@ibp.ac.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding
chemical_list: C507017:ACAP1 protein, human; D020690:GTPase-Activating Proteins