title: Molecular mechanism of membrane constriction and tubulation mediated by the F-BAR protein Pacsin/Syndapin.
abstract: Peripheral membrane proteins of the Bin/amphiphysin/Rvs (BAR) and Fer-CIP4 homology-BAR (F-BAR) family participate in cellular membrane trafficking and have been shown to generate membrane tubules. The degree of membrane bending appears to be encoded in the structure and immanent curvature of the particular protein domains, with BAR and F-BAR domains inducing high- and low-curvature tubules, respectively. In addition, oligomerization and the formation of ordered arrays influences tubule stabilization. Here, the F-BAR domain-containing protein Pacsin was found to possess a unique activity, creating small tubules and tubule constrictions, in addition to the wide tubules characteristic for this subfamily. Based on crystal structures of the F-BAR domain of Pacsin and mutagenesis studies, vesiculation could be linked to the presence of unique structural features distinguishing it from other F-BAR proteins. Tubulation was suppressed in the context of the full-length protein, suggesting that Pacsin is autoinhibited in solution. The regulated deformation of membranes and promotion of tubule constrictions by Pacsin suggests a more versatile function of these proteins in vesiculation and endocytosis beyond their role as scaffold proteins.
authors: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors: Qi
authors: Q
authors: Wang
authors: Marcos V A S
authors: MV
authors: Navarro
authors: Gary
authors: G
authors: Peng
authors: Evan
authors: E
authors: Molinelli
authors: Shih Lin
authors: SL
authors: Goh
authors: Bret L
authors: BL
authors: Judson
authors: Kanagalaghatta R
authors: KR
authors: Rajashankar
authors: Holger
authors: H
authors: Sondermann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D003460:Crystallization; D004705:Endocytosis; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008081:Liposomes; C492182:PACSIN1 protein, human; C120714:PACSIN2 protein, human