Conserved pore‐forming regions in polypeptide‐ transporting proteins

Abstract

Transport of solutes or macromolecules such as proteins across membranes requires a proteinaceous channel or transporter. Besides their way of action, these proteins can be divided according to their substrates or to their secondary structure of the membrane domain. In terms of secondary structure a-helical or b-sheet channels can be differentiated [1]. Both types of channels show a high neighbourhood correlation according to the fold [2] suggesting similar folds of the membrane inserted domains. In the past, much attention was given to the a-helical channels [3-5]. However, recently ion channels formed by the b-sheets moved into the focus of interest [6,7]. While analyzing these channels it became obvious that they emerged from outer membrane proteins of prokaryotic endo-symbionts, as these proteins were the only b-barrel type membrane proteins found in bacteria [6]. This class of proteins is present in organellar membranes of eukaryotic organisms, like in the outer mitochondrial membrane [8] emerged from a-proteobacteria [9], in the outer envelope of chloroplasts [10,11] emerged from cyanobacteria [9] and maybe even in the peroxi-somal membrane [12]. The peroxisomal b-barrel protein might be an indication either of the discussed endosymbiotic origin (for example [13]) or of a redistribution of proteins within the cell as a result of the gene transfer of the other two endosymbiotic events [14]. Most of the b-barrel type channels of eukaryotes belong to the porin type family. Recent research revealed that b-barrel type channels are also involved in the translocation of polypeptides [15], in the assembly of proteins in the outer membrane of endosymbio-tic organelles [16-19] or in the assembly of proteins in the outer membrane of bacteria [7,20,21]. One polypeptide-transporter that was found in Bordetella pertussis is FhaC, which secretes the main Transport of solutes and polypeptides across membranes is an essential process for every cell. In the past, much focus has been placed on helical transporters. Recently, the b-barrel-shaped transporters have also attracted some attention. The members of this family are found in the outer bacterial membrane and the outer membrane of endosymbiotically derived organ-elles. Here we analyze the features and the evolutionary development of a specified translocator family, namely the b-barrel-shaped polypeptide-transporters. We identified sequence motifs, which characterize all transporters of this family, as well as motifs specific for a certain subgroup of proteins of this class. The general motifs are related to the structural composition of the pores. Further analysis revealed a defined distance of two motifs to the C-terminal portion of the proteins. Furthermore, the evolutionary relationship of the proteins and the motifs are discussed. Abbreviation EBS, exact b-sheet.

Granzyme B enters the mitochondria in a Sam50-, Tim22- and mtHsp70-dependent manner to induce apoptosis

“…However, GB KR/AA, which cannot enter the mitochondria is significantly impaired in its ability to trigger ROS and cell death both in vitro and in vivo, indicating that GB mitochondrial entry is necessary for efficient cell death induction in agreement with Jacquemin et al 18 Tob55/Sam50 belongs to the bacterial β-barrel-shaped channels of the Omp85 family. 58,59 The primary function of this protein family is to integrate β-barrel proteins into the outer membranes of bacteria or mitochondria. However, Toc75, the central import pore of the translocase of the outer membrane of chloroplasts, also belongs to the Omp85 family, implying that proteins structurally similar to Tob55/Sam50 can function as transport pores.…”

Functional and Phylogenetic Properties of the Pore-forming β-Barrel Transporters of the Omp85 Family

“…The PTBs are partitioned into two functional categories, namely in translocation of precursor proteins across the membrane and in the assembly of outer membrane proteins (3). Furthermore, comparison between chloroplastic, mitochondrial, and bacterial Omp85 protein sequences revealed a high similarity of these PTBs (14,16,17).The PTB Toc75 forms a complex with Toc34, Toc64, and Toc159 (3). A precursor protein-binding site at Toc75 (15, 18), together with the action of Toc159 (19), facilitates the translocation of precursor proteins across the membrane.…”

“…The PTBs are partitioned into two functional categories, namely in translocation of precursor proteins across the membrane and in the assembly of outer membrane proteins (3). Furthermore, comparison between chloroplastic, mitochondrial, and bacterial Omp85 protein sequences revealed a high similarity of these PTBs (14,16,17).…”

Chloroplast Omp85 proteins change orientation during evolution

“…As mentioned, chloroplasts have two families of Omp85 homologs (1,22). Toc75-V (for translocon of the outer envelope membrane of chloroplast protein of 75 kDa encoded on the fifth chromosome in Arabidopsis thaliana; also termed Oep66 or Oep80 for outer envelope protein of 66/80 kDa in Pisum sativum/A.…”