The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans-membrane topology

Abstract

The amino acid distribution in membrane spanning segments and connecting loops in bacterial inner membrane proteins was analysed. The basic residues Arg and Lys are four times less prevalent in periplasmic as compared to cytosolic connecting loops, whereas no comparable effect is observed for the acidic residues Asp and Glu. Also, Pro is shown to be tolerated to a much larger extent in membrane spanning segments with their N‐terminus pointing towards the cytosol than in those with the opposite orientation. The significance of these findings with regard to the mechanism of biogenesis of bacterial inner membrane proteins is discussed.

Topology prediction for helical transmembrane proteins at 86% accuracy–Topology prediction at 86% accuracy

“…Prediction methods were designed to predict the locations of HTMs (von Heijne, 1981(von Heijne, , 1986a(von Heijne, , 1986b(von Heijne, , 1992Argos et al, 1982;Kyte & Doolittle, 1982;Engelman et al, 1986;Cornette et al, 1987;von Heijne & Gavel, 1988;Degli Esposti et al, 1990;von Heijne & Manoil, 1990;Landolt-Marticorena et al, 1992;Donnelly et al, 1993;Edelman, 1993;O'Hara et al, 1993;Sipos & von Heijne, 1993;Jones et al, 1994;Persson & Argos, 1994;Donnelly & Findlay, 1995; and the orientation of HTMs with respect to the cell (dubbed topology, Fig. 1; von Heijne & Gavel, 1988;von Heijne, 1989von Heijne, , 1992Nilsson & von Heijne, 1990;Sipos & von Heijne, 1993;Jones et al, 1994;.…”

Conserved amino acid residues found in a predicted cytosolic domain of the lipopolysaccharide biosynthetic protein WecA are implicated in the recognition of UDP-N-acetylglucosamine

“…1a). The prediction also includes topological information on the orientation of the transmembrane helices, which is based on the fact that the positively charged residues arginine and lysine are mainly found in non-transmembrane parts of the protein on the cytoplasmic side (von Heijne, 1986(von Heijne, , 1997). The predicted model for the topology of WecA was compared with that of the E. coli MraY protein (Fig.…”

Secondary solute transport in bacteria

“…(vi) A relatively large cytoplasmic loop separates the helices I-VI from helices VII-XII. (vii) A surplus of positively charged amino acid residues (Arg, Lys and His) is found in cytoplasmic loops (the 'positive inside' rule [116,117]). (viii) Only a few charged residues are present in membrane spanning segments, and these may be tolerated in these hydrophobic regions by forming salt bridges that are energetically more favourable than the presence of the 'free' polar side-chains (see subsection IV-B) or by forming part of a hydrophilic pocket that interacts with the ligand(s) (see Section VII).…”