A general amphipathic α-helical motif for sensing membrane curvature

The Golgi-associated protein ArfGAP1 has an unusual membrane-adsorbing amphipathic α-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 α-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 β-propeller structure. Ser/Thr-rich amphipathic helices thus define a general motif used by proteins of various functions for sensing membrane curvature.

[1]  David Eisenberg,et al.  The helical hydrophobic moment: a measure of the amphiphilicity of a helix , 1982, Nature.

[2]  J. Rothman,et al.  Hydrolysis of bound GTP by ARF protein triggers uncoating of Golgi- derived COP-coated vesicles , 1993, The Journal of cell biology.

[3]  G M Anantharamaiah,et al.  Interactions of synthetic peptide analogs of the class A amphipathic helix with lipids. Evidence for the snorkel hypothesis. , 1994, The Journal of biological chemistry.

[4]  M. Bornens,et al.  A peripheral protein associated with the cis-Golgi network redistributes in the intermediate compartment upon brefeldin A treatment , 1994, The Journal of cell biology.

[5]  M. Fang,et al.  Kes1p shares homology with human oxysterol binding protein and participates in a novel regulatory pathway for yeast Golgi‐derived transport vesicle biogenesis. , 1996, The EMBO journal.

[6]  A. Tracey,et al.  Structure of the membrane binding domain of CTP:phosphocholine cytidylyltransferase. , 1996, Biochemistry.

[7]  V. Mishra,et al.  Interaction of model class A1, class A2, and class Y amphipathic helical peptides with membranes. , 1996, Biochemistry.

[8]  B. Antonny,et al.  N-terminal hydrophobic residues of the G-protein ADP-ribosylation factor-1 insert into membrane phospholipids upon GDP to GTP exchange. , 1997, Biochemistry.

[9]  B. Antonny,et al.  Activation of ADP-ribosylation Factor 1 GTPase-Activating Protein by Phosphatidylcholine-derived Diacylglycerols* , 1997, The Journal of Biological Chemistry.

[10]  S H White,et al.  Hydrophobic interactions of peptides with membrane interfaces. , 1998, Biochimica et biophysica acta.

[11]  M. Bornens,et al.  GMAP-210, A Cis-Golgi Network-associated Protein, Is a Minus End Microtubule-binding Protein , 1999, The Journal of cell biology.

[12]  M. Dathe,et al.  Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells. , 1999, Biochimica et biophysica acta.

[13]  N. Ben-Tal,et al.  Electrostatic properties of membranes containing acidic lipids and adsorbed basic peptides: theory and experiment. , 1999, Biophysical journal.

[14]  J. Rothman,et al.  Coupling of Coat Assembly and Vesicle Budding to Packaging of Putative Cargo Receptors , 1999, Cell.

[15]  S. White,et al.  An amphipathic alpha-helix at a membrane interface: a structural study using a novel X-ray diffraction method. , 1999, Journal of molecular biology.

[16]  William F. DeGrado,et al.  Asparagine-mediated self-association of a model transmembrane helix , 2000, Nature Structural Biology.

[17]  D. Engelman,et al.  Interhelical hydrogen bonding drives strong interactions in membrane proteins , 2000, Nature Structural Biology.

[18]  N. Sreerama,et al.  Estimation of protein secondary structure from circular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set. , 2000, Analytical biochemistry.

[19]  J. Weissman,et al.  A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Ming-Ming Zhou.  Phosphothreonine recognition comes into focus , 2000, Nature Structural Biology.

[21]  P. De Camilli,et al.  Generation of high curvature membranes mediated by direct endophilin bilayer interactions , 2001, The Journal of cell biology.

[22]  N. Daigle,et al.  An evolutionarily conserved NPC subcomplex, which redistributes in part to kinetochores in mammalian cells , 2001, The Journal of cell biology.

[23]  G. Prestwich,et al.  Analysis of oxysterol binding protein homologue Kes1p function in regulation of Sec14p-dependent protein transport from the yeast Golgi complex , 2002, The Journal of cell biology.

[24]  Ian G. Mills,et al.  Curvature of clathrin-coated pits driven by epsin , 2002, Nature.

[25]  Activity of specific lipid-regulated ADP ribosylation factor-GTPase-activating proteins is required for Sec14p-dependent Golgi secretory function in yeast. , 2002, Molecular biology of the cell.

[26]  L. Johannes,et al.  The Overexpression of GMAP‐210 Blocks Anterograde and Retrograde Transport Between the ER and the Golgi Apparatus , 2002, Traffic.

[27]  M. Hetzer,et al.  The Conserved Nup107-160 Complex Is Critical for Nuclear Pore Complex Assembly , 2003, Cell.

[28]  Bruno Antonny,et al.  Lipid packing sensed by ArfGAP1 couples COPI coat disassembly to membrane bilayer curvature , 2003, Nature.

[29]  V. Olkkonen,et al.  The OSBP-related proteins: a novel protein family involved in vesicle transport, cellular lipid metabolism, and cell signalling. , 2003, Biochimica et biophysica acta.

[30]  F. Barr,et al.  Golgins in the structure and dynamics of the Golgi apparatus. , 2003, Current opinion in cell biology.

[31]  E. Zimmerman,et al.  Removal of a single pore subcomplex results in vertebrate nuclei devoid of nuclear pores. , 2003, Molecular cell.

[32]  S. Munro,et al.  The GTPase Arf1p and the ER to Golgi cargo receptor Erv14p cooperate to recruit the golgin Rud3p to the cis-Golgi , 2004, The Journal of cell biology.

[33]  Ralf Langen,et al.  Structure of membrane-bound alpha-synuclein studied by site-directed spin labeling. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Ralf Langen,et al.  Structure of membrane-bound α-synuclein studied by site-directed spin labeling , 2004 .

[35]  J. Seelig.  Thermodynamics of lipid-peptide interactions. , 2004, Biochimica et biophysica acta.

[36]  G. Blobel,et al.  Structural and functional analysis of Nup133 domains reveals modular building blocks of the nuclear pore complex , 2004, The Journal of cell biology.

[37]  I. Mills,et al.  COP and clathrin-coated vesicle budding: different pathways, common approaches. , 2004, Current opinion in cell biology.

[38]  Michel Bornens,et al.  GMAP-210 Recruits γ-Tubulin Complexes to cis-Golgi Membranes and Is Required for Golgi Ribbon Formation , 2004, Cell.

[39]  G. Drin,et al.  ArfGAP1 responds to membrane curvature through the folding of a lipid packing sensor motif , 2005, The EMBO journal.

[40]  Randy Schekman,et al.  Sar1p N-Terminal Helix Initiates Membrane Curvature and Completes the Fission of a COPII Vesicle , 2005, Cell.

[41]  James H. Hurley,et al.  Structural mechanism for sterol sensing and transport by OSBP-related proteins , 2005, Nature.

[42]  B. Antonny,et al.  Real-time assays for the assembly-disassembly cycle of COP coats on liposomes of defined size. , 2005, Methods in enzymology.

[43]  Ralf Langen,et al.  Mechanism of endophilin N‐BAR domain‐mediated membrane curvature , 2006, The EMBO journal.

[44]  B. Antonny.  Membrane deformation by protein coats. , 2006, Current opinion in cell biology.

[45]  J. Hurley,et al.  Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein–related proteins and phosphoinositides , 2006, The Journal of cell biology.

[46]  Soichi Takeda,et al.  Endophilin BAR domain drives membrane curvature by two newly identified structure‐based mechanisms , 2006, The EMBO journal.

[47]  Gilbert Deléage,et al.  Prediction of amphipathic in-plane membrane anchors in monotopic proteins using a SVM classifier , 2006, BMC Bioinformatics.

[48]  M. Rotman,et al.  Golgi Localization Determinants in ArfGAP1 and in New Tissue-specific ArfGAP1 Isoforms* , 2006, Journal of Biological Chemistry.

[49]  G. Drin,et al.  Two lipid-packing sensor motifs contribute to the sensitivity of ArfGAP1 to membrane curvature. , 2007, Biochemistry.