A general amphipathic α-helical motif for sensing membrane curvature

  title={A general amphipathic $\alpha$-helical motif for sensing membrane curvature},
  author={Guillaume Drin and J F Casella and Romain Gautier and Thomas Boehmer and Thomas U. Schwartz and Bruno Antonny},
  journal={Nature Structural \&Molecular Biology},
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… 

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Membrane Curvature Sensing by Amphipathic Helices

It is revealed that both the hydrophobic and hydrophilic faces of the helix greatly influence binding and sensing, suggesting that the description of membrane curvature-sensing requires consideration of several factors such as short and long range electrostatic interactions, hydrogen bonding, and the volume and structure of insertedHydrophobic residues.

How curved membranes recruit amphipathic helices and protein anchoring motifs.

Lipids and several specialized proteins are thought to be able to sense the curvature of membranes (MC). Here we used quantitative fluorescence microscopy to measure curvature-selective binding of

Membrane Curvature Sensing by Amphipathic Helices Is Modulated by the Surrounding Protein Backbone

The resulting chimeras recapitulated the original proteins localization, indicating that ALPS motifs are sufficient to specifically localize proteins, which can be further modulated by the surrounding protein backbone.

A conserved amphipathic helix is required for membrane tubule formation by Yop1p

The secondary structure and dynamics of the DP1 family protein produced from the YOP1 gene is characterized and a C-terminal conserved amphipathic helix (APH) that is necessary for membrane tubule formation is identified, indicating that APHs play a previously unrecognized role in RHD membrane curvature stabilization.

Amphipathic motifs in BAR domains are essential for membrane curvature sensing

BAR (Bin/Amphiphysin/Rvs) domains and amphipathic α‐helices (AHs) are believed to be sensors of membrane curvature thus facilitating the assembly of protein complexes on curved membranes. Here, we

Preferred Binding Mechanism of Osh4's Amphipathic Lipid-Packing Sensor Motif, Insights from Molecular Dynamics.

Extended all-atom molecular dynamics is used to study the binding mechanism and conformation of the N-terminus of the lipid-transport protein Osh4 in yeast, showing that the ALPS peptide is more likely to bind membrane surfaces with packing defects and higher anionic character.



Two lipid-packing sensor motifs contribute to the sensitivity of ArfGAP1 to membrane curvature.

The results suggest that depending on the engagement of one or two functional ALPS motifs, ArfGAP1 can respond to a wide range of membrane curvature and can adapt to lipid membranes of various acyl chain compositions.

ArfGAP1 responds to membrane curvature through the folding of a lipid packing sensor motif

It is shown that a central sequence of about 40 amino acids in ArfGAP1 acts as a lipid‐packing sensor, and site‐directed mutagenesis, limited proteolysis and circular dichroism experiments suggest that the ALPS motif, which is unstructured in solution, inserts bulky hydrophobic residues between loosely packed lipids and forms an amphipathic helix on highly curved membranes.

An amphipathic alpha-helix at a membrane interface: a structural study using a novel X-ray diffraction method.

The first results of an effort to obtain detailed structural information about alpha-helices in membranes by means of a novel X-ray diffraction method are reported, determining the transbilayer position and orientation of an archetypal class A amphipathic helical peptide in oriented fluid-state dioleoylphosphatidylcholine (DOPC) bilayers.

Asparagine-mediated self-association of a model transmembrane helix

Interactions involving a polar Asn side chain provide a strong thermodynamic driving force for membrane helix association within a membrane-like environment.

Mechanism of endophilin N‐BAR domain‐mediated membrane curvature

The crystal structure of rat endophilin‐A1 BAR domain is solved and a distinctive insert protruding from the membrane interaction face is examined, predicted to form an additional amphipathic helix and important for curvature generation.

Structure of the membrane binding domain of CTP:phosphocholine cytidylyltransferase.

It has been proposed that the domain of the regulatory enzyme, CTP:phosphocholine cytidylyltransferase, which mediates reversible binding of the enzyme to membranes, is an amphipathic alpha-helix of

Interhelical hydrogen bonding drives strong interactions in membrane proteins

It is found in both detergent miscelles and biological membranes that helix association is driven strongly by asparagine, independent of the rest of the hydrophobic leucine and/or valine sequence, and membrane proteins may fold to avoid exposure of strongly hydrogen bonding groups at their lipid exposed surfaces.

N-terminal hydrophobic residues of the G-protein ADP-ribosylation factor-1 insert into membrane phospholipids upon GDP to GTP exchange.

The binding of ARF to model unilamellar vesicles of defined composition strongly suggests that, upon GDP/GTP exchange, the N-terminal helix is released from the protein core so its hydrophobic residues can interact with membrane phospholipids.

Curvature of clathrin-coated pits driven by epsin

It is shown here that epsin 1 directly modifies membrane curvature on binding to PtdIns(4,5)P2 in conjunction with clathrin polymerization, and it is proposed that this helix is inserted into one leaflet of the lipid bilayer, inducing curvature.