Prediction of amphipathic in-plane membrane anchors in monotopic proteins using a SVM classifier

Abstract

Background: Membrane proteins are estimated to represent about 25% of open reading frames in fully sequenced genomes. However, the experimental study of proteins remains difficult. Considerable efforts have thus been made to develop prediction methods. Most of these were conceived to detect transmembrane helices in polytopic proteins. Alternatively, a membrane protein can be monotopic and anchored via an amphipathic helix inserted in a parallel way to the membrane interface, so-called in-plane membrane (IPM) anchors. This type of membrane anchor is still poorly understood and no suitable prediction method is currently available.

Nucleoid occlusion protein N oc recruits DNA to the bacterial cell membrane

“…Analysis of Noc using AMPHIPASEEK, a program designed to look for amphipathic in-plane membrane anchors (Sapay et al , 2006), highlighted a possible N-terminal amphipathic helix (Fig 2A). A helical wheel projection of the N-terminus (aa 1–14) broadly conforms to the canonical organisation of an amphipathic helix, with a hydrophobic face opposed by a more polar one and with positively charged residues flanking the hydrophobic face (Fig 2B).…”

SepF Increases the Assembly and Bundling of FtsZ Polymers and Stabilizes FtsZ Protofilaments by Binding along Its Length

“…The bioinformatic analysis of SepF amino acid sequence did not reveal the presence of a transmembrane helix. However, the presence of an in-plane membrane anchor, spanning N-terminal amino acid residues (KDKLKN 7 ), was predicted in SepF sequence by AmphipaSeek program (38) Analogous to SepF, another cytosolic protein, ZapA, has been shown to promote the assembly and bundling of FtsZ and to colocalize with the Z-ring in vivo (12). The functional overlap of SepF with FtsA and ZapA suggests that SepF can act during the early events of cell division because both ZapA and FtsA support the assembly of the Z-ring during the early stages of the cell division.…”

Combined use of mass spectrometry and heterologous expression for identification of membrane-interacting peptides in cytochrome P450 46A1 and NADPH-cytochrome P450 oxidoreductase

“…This includes transmembrane segments [7], covalent links to a hydrophobic compound [8], electrostatic binding to phospholipid head groups [9], as well as hydrophobic loops and amphiphilic helices peripherally associated with the membrane [3, 4, 10]. The transmembrane segments are the most studied because they can be easily predicted from the sequence hydropathy plots.…”

“…Results of such predictions are usually in a good agreement with experimental data. Computing of the membrane interactions other than transmembrane spanning is more difficult because of the diversity of interactions and limited experimental information available [4-6]. The latter hampers our understanding how membrane proteins function and requires development of new approaches to study membrane topology.…”