Transport protein evolution deduced from analysis of sequence, topology and structure

Abstract

The vast majority of well studied transmembrane channels, secondary carriers, primary active transporters and group translocators are believed to have arisen vis intragenic duplication events from simple channel-forming peptides with just 1–3 transmembrane α-helical segments, found ubiquitously in nature. Only a few established channel-forming proteins appear to have evolved via other pathways. The proposed pathway for the evolutionary appearance of the five types of transport proteins involved intragenic duplication of transmembrane pore-forming peptide-encoding genes, giving rise to channel proteins. These gave rise to single protein secondary carriers which upon superimposition of addition protein domains and proteins, including energy-coupling proteins and extracytoplasmic receptors, gave rise to multidomain, multicomponent carriers, primary active transporters and group translocators. Some of the largest and best characterized superfamilies of these transmembrane transport proteins are discussed from topological and evolutionary standpoints.

Pseudo-Symmetric Assembly of Protodomains as a Common Denominator in the Evolution of Polytopic Helical Membrane Proteins

“…One can also envision the formation of a 7TMH domain from the duplication and fusion of two 4TMH protodomains with the attrition of one helix at the N or C terminus or possibly in the middle. The duplication fusion event that may well have originally duplicated a 4TMH protodomain rather than 3TMH has been previously suggested for GPCRs (Saier 2016;Yee et al 2013).…”

“…2d). Using this notation it is easy to find topological similarities across different proteins, but also to distinguish them, if there is any way to relate these domains, as has been done in the literature (Jaehme et al 2015(Jaehme et al , 2016Saier 2016;Yee et al 2013), one may invoke a "conformational evolution" mechanism (see later).…”

Energetic Evolution of Cellular Transportomes

“…The tightening of porous and leaky primordial envelopes such that they did not let in (and could learn to efflux) all kinds of substances [13,14] has been proposed as a turning point for membrane transporters to co-evolve together with lipid bilayer membranes [15]. Different classes of transporters, each including several transporter superfamilies, share a common ancestral family of peptides which carry 1-4 transmembrane domains and form homo-and heterooligomer channels [16][17][18][19]. Intragenic duplication and triplication have been the major events promoting the diversification of transporter proteins [17,19].…”

An EmrB multidrug efflux pump in Burkholderia thailandensis with unexpected roles in antibiotic resistance

“…Many pathogenic Burkholderia species exhibit inherent resistance to a wide range of antibiotics and disinfectants (3). Efflux systems involved in antibiotic resistance include the resistancenodulation-division (RND) efflux systems and the E. coli multidrug resistance B (EmrB) family transporters (3)(4)(5). Extensively studied pathogens include Burkholderia pseudomallei, a soil saprophyte causing melioidosis, and its clonal derivative Burkholderia mallei, a host-adapted pathogen, which is the causative agent of glanders (6).…”