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Of the membrane proteins of known structure, we found that a remarkable 67% of the water soluble domains are structurally similar to water soluble proteins of known structure. Moreover, 41% of known water soluble protein structures share a domain with an already known membrane protein structure. We also found that functional residues are frequently conserved between extramembrane domains of membrane and soluble proteins that share structural similarity. These results suggest membrane and soluble proteins readily exchange domains and their attendant functionalities. The exchanges between membrane and soluble proteins are particularly frequent in eukaryotes, indicating that this is an important mechanism for increasing functional complexity. The high level of structural overlap between the two classes of proteins provides an opportunity to employ the extensive information on soluble proteins to illuminate membrane protein structure and function, for which much less is known. To this end, we employed structure guided sequence alignment to elucidate the functions of membrane proteins in the human genome. Our results bridge the gap of fold space between membrane and water soluble proteins and provide a resource for the prediction of membrane protein function. A database of predicted structural and functional relationships for proteins in the human genome is provided at sbi.postech.ac.kr/emdmp.

Gene essentiality changes are crucial for organismal evolution. However, it is unclear how essentiality of orthologs varies across species. We investigated the underlying mechanism of gene essentiality changes between yeast and mouse based on the framework of network evolution and comparative genomic analysis. We found that yeast nonessential genes become essential in mouse when their network connections rapidly increase through engagement in protein complexes. The increased interactions allowed the previously nonessential genes to become members of vital pathways. By accounting for changes in gene essentiality, we firmly reestablished the centrality-lethality rule, which proposed the relationship of essential genes and network hubs. Furthermore, we discovered that the number of connections associated with essential and non-essential genes depends on whether they were essential in ancestral species. Our study describes for the first time how network evolution occurs to change gene essentiality.

Although a number of studies have reported that resveratrol has analgesic effects, the direct effect of resveratrol on substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) involved in orofacial nociceptive transmission has not been clearly examined. Thus, the objective of this study was to investigate effects of resveratrol on SG neurons of Vc in mice using a whole-cell patch-clamp technique. Resveratrol (500 μM) induced repeatable inward currents without desensitisation. Resveratrol-induced inward currents were shown in a concentration-dependent manner. Resveratrol-induced responses were sustained in the presence of tetrodotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and DL-2-Amino-5-phosphonovaleric acid (DL-AP5). However, resveratrol-induced inward currents were suppressed in the presence of picrotoxin and strychnine. These results indicate that resveratrol can directly act on SG neurons of Vc with possible inhibitory effects on SG neurons through activation of GABAA receptors and/or glycine receptors. Thus, resveratrol can be a potential therapeutic for orofacial pain modulation. [ABSTRACT FROM AUTHOR]

ABCG subfamily proteins are highly enriched in terrestrial plants. Many of these proteins secrete secondary metabolites that repel or inhibit pathogens. To establish why the ABCG subfamily proteins proliferated extensively during evolution, we constructed phylogenetic trees from a broad range of eukaryotic organisms. ABCG proteins were massively duplicated in land plants and in oomycetes, a group of agronomically important plant pathogens, which prompted us to hypothesize that plant and pathogen ABCGs coevolved. Supporting this hypothesis, full‐size ABCGs in host plants (Arabidopsis thaliana and Glycine max) and their pathogens (Hyaloperonospora arabidopsidis and Phytophthora sojae, respectively) had similar divergence times and patterns. Furthermore, generalist pathogens with broad ranges of host plants have diversified more ABCGs than their specialist counterparts. The hypothesis was further tested using an example pair of ABCGs that first diverged during multiplication in a host plant and its pathogen: AtABCG31 of A. thaliana and HpaP802307 of H. arabidopsidis. AtABCG31 expression was activated following infection with H. arabidopsidis, and disrupting AtABCG31 led to increased susceptibility to H. arabidopsidis. Together, our results suggest that ABCG genes in plants and their oomycete pathogens coevolved in an arms race, to extrude secondary metabolites involved in the plant's defense response against pathogens. [ABSTRACT FROM AUTHOR]