A general amphipathic alpha-helical motif for sensing membrane curvature.
The Golgi-associated protein ArfGAP1 has an unusual membrane-adsorbing amphipathic alpha-helix: its polar face is weakly charged, containing mainly serine and threonine residues. We show that this feature explains the specificity of ArfGAP1 for curved versus flat lipid membranes. We built an algorithm to identify other potential amphipathic alpha-helices rich in serine and threonine residues in protein databases. Among the identified sequences, we show that three act as membrane curvature sensors. In the golgin GMAP-210, the sensor may serve to trap small vesicles at the end of a long coiled coil. In Osh4p/Kes1p, which transports sterol between membranes, the sensor controls access to the sterol-binding pocket. In the nucleoporin Nup133, the sensor corresponds to an exposed loop of a beta-propeller structure. Ser/Thr-rich amphipathic helices thus define a general motif used by proteins of various functions for sensing membrane curvature.
Drin
Guillaume
G
Centre National de la Recherche Scientifique (CNRS), Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis, 06560 Valbonne, France.
Casella
Jean-François
JF
Gautier
Romain
R
Boehmer
Thomas
T
Schwartz
Thomas U
TU
Antonny
Bruno
B
D000465:Algorithms; D020816:Amino Acid Motifs; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D019295:Computational Biology; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins / Q000737:chemistry*; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D008958:Models, Molecular; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D051381:Rats; D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics; D012694:Serine / Q000737:chemistry; D013912:Threonine / Q000737:chemistry; D000098825:Oxysterol Binding Proteins
D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D008081:Liposomes; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D013912:Threonine; C503239:Arfgap1 protein, rat; C087901:KES1 protein, S cerevisiae; D000098825:Oxysterol Binding Proteins; C440250:NUP133 protein, human; C109331:TRIP11 protein, human