The general protein secretory pathway: phylogenetic analyses leading to evolutionary conclusions

Abstract

We have identified all homologues in the current databases of the ubiquitous protein constituents of the general secretory (Sec) pathway. These prokaryotic/eukaryotic proteins include (1) SecY/Sec61alpha, (2) SecE/Sec61gamma, (3) SecG/Sec61beta, (4) Ffh/SRP54 and (5) FtsY/SRP receptor subunit-alpha. Phylogenetic and sequence analyses lead to major conclusions concerning (1) the ubiquity of these proteins in living organisms, (2) the topological uniformity of some but not other Sec constituents, (3) the orthologous nature of almost all of them, (4) a total lack of paralogues in almost all organisms for which complete genome sequences are available, (5) the occurrence of two or even three paralogues in a few bacteria, plants, and yeast, depending on the Sec constituent, and (6) a tremendous degree of sequence divergence in bacteria compared with that in archaea or eukaryotes. The phylogenetic analyses lead to the conclusion that with a few possible exceptions, the five families of Sec constituents analyzed generally underwent sequence divergence in parallel but at different characteristic rates. The results provide evolutionary insights as well as guides for future functional studies. Because every organism with a fully sequenced genome exhibits at least one orthologue of each of these Sec proteins, we conclude that all living organisms have relied on the Sec system as their primary protein secretory/membrane insertion system. Because most prokaryotes and many eukaryotes encode within their genomes only one of each constituent, we also conclude that strong evolutionary pressure has minimized gene duplication events leading to the establishment of Sec paralogues. Finally, the sequence diversity of bacterial proteins as compared with their archaeal and eukaryotic counterparts is in agreement with the suggestion that bacteria were the evolutionary predecessors of archaea and eukaryotes.

Agrobacterium tumefaciens VirB6 Domains Direct the Ordered Export of a DNA Substrate Through a Type IV Secretion System

“…33,46 Such an activity is reminiscent of known or postulated roles of polytopic subunits of dedicated protein translocation pathways in bacteria as well as eukaryotic cells. 47,48 Curiously, however, our TrIP studies identified loop P2 and not the TMS or cytoplasmic loops as necessary for the VirB6-substrate close contact. Loop P2 might thus form part of the channel architecture, embedding into the channel either stably or dynamically as a function of substrate transfer.…”

Identification of Two Interaction Sites in SecY that Are Important for the Functional Interaction with SecA

“…33 Third, replacement of six residues just preceding TMS4c (Leu164-Met169) by an unrelated polypeptide stretch strongly interferes with protein translocation. 34 The region following TMS4c (Gly182-Pro200) is the most conserved region of the SecY/Sec61α family, 35 that has been proposed to form a hinge region for separation of the two domains of the channel. 12 The data presented here provide clues on how the conformational changes of SecA could result in opening of the SecYEG channel.…”

Streptococcal viability and diminished stress tolerance in mutants lacking the signal recognition particle pathway or YidC2

“…The SRP pathway is conserved in all domains of life and has been considered crucial for the vitality of all organisms (2)(3)(4)(5)(6). Saccharomyces cerevisiae represents the only known example of an organism able to endure mutations within the SRP pathway (7).…”

“…Mutants are exceedingly sick and adapt physiologically by repression of protein synthesis, induction of heat shock genes, and dramatic slow-down of growth (8). Comparative phylogenetic analyses demonstrate that genomes of Eukaryotes, Archaea, and Bacteria encode at a minimum the SRP components SRP54 protein, known in Eubacteria as Ffh (54-kDa homolog), and a 4.5 or 7S small cytoplasmic RNA (scRNA) (5). The third universally conserved element of the pathway is the SRP receptor subunit (SR␣), or in Escherichia coli, FtsY (9).…”