Biomedical subjects

Ming-Ren Yen

Publications and source records attributed to Ming-Ren Yen.

9 recordsLinked to original sources

PubMed2026

Protocol to predict gene expression from transcriptomic data using PREDICT.

Linking DNA sequence variation to context-specific transcriptional programs is a critical challenge in regulatory genomics, especially for non-model organisms. Here, we present PREDICT, a modular Python package for discovering cis-regulatory elements and transcription factor binding motifs. We describe steps to identify enriched k-mers from differentially expressed genes, map them to known motifs, quantify their impact on gene expression, and visualize motif co-occurrences. PREDICT provides a robust, k-mer-based approach to uncover regulatory logic in diverse genomic systems. For complete details on the use and execution of this protocol, please refer to Yen et al. and Liu et al.1,2.

Gene Expression Profiling↗

PubMed2006

Topological predictions for integral membrane permeases of the phosphoenolpyruvate:sugar phosphotransferase system.

We report bioinformatic analyses of the largest superfamily of integral membrane permeases of the bacterial phosphotransferase system (PTS), the Enzyme IIC constituents of the Glc superfamily. Phylogenetic analyses reveal that this superfamily consists of five equally distant families, the Glucose (Glc), beta-Glucoside (Bgl), Fructose (Fru), Mannitol (Mtl) and Lactose (Lac) families. Average hydropathy, amphipathicity and similarity plots were generated for these five families as well as for the entire superfamily. Charged residue distribution was analyzed, and the most conserved sequence motif, common to all five families, was identified. The results show that the members of all five families exhibit similar average hydropathy plots with regions of average amphipathicity and relative conservation also being similar. Evidence is presented suggesting that the Glucitol (Gut) family of Enzyme IIC constituents is a distant member of the Glc superfamily. Based on our analyses we offer a topological model that resembles, but differs in detail from the two previously proposed models.

Amino Acid Sequence↗

PubMed2004

The YedZ family: possible heme binding proteins that can be fused to transporters and electron carriers.

YedZ of Escherichia coli is an integral 6 transmembrane spanning (TMS) protein of unknown function. We have identified homologues of YedZ in bacteria and animals but could not find homologues in Archaea or the other eukaryotic kingdoms. YedZ homologues exhibit conserved histidyl residues in their transmembrane domains that may function in heme binding. Some of the homologues encoded in the genomes of magnetotactic bacteria and cyanobacteria have YedZ domains fused to transport and electron transfer proteins, respectively. One of the animal homologues is the 6 TMS epithelial plasma membrane antigen of the prostate (STAMP1) that is overexpressed in prostate cancer. Animal homologues have YedZ domains fused C-terminal to homologues of coenzyme F420-dependent NADP oxidoreductases. YedZ homologues are shown to have arisen by intragenic triplication of a 2 TMS-encoding element. They exhibit slight but statistically significant sequence similarity to two families of putative heme export systems and one family of cytochrome-containing electron carriers. We propose that YedZ homologues function as heme-binding proteins that can facilitate or regulate oxidoreduction, transmembrane electron flow and transport.

Amino Acid Motifs↗

PubMed2003

Type II protein secretion and its relationship to bacterial type IV pili and archaeal flagella.

Homologues of the protein constituents of the Klebsiella pneumoniae (Klebsiella oxytoca) type II secreton (T2S), the Pseudomonas aeruginosa type IV pilus/fimbrium biogenesis machinery (T4P) and the Methanococcus voltae flagellum biogenesis machinery (Fla) have been identified. Known constituents of these systems include (1). a major prepilin (preflagellin), (2). several minor prepilins (preflagellins), (3). a prepilin (preflagellin) peptidase/methylase, (4). an ATPase, (5). a multispanning transmembrane (TM) protein, (6). an outer-membrane secretin (lacking in Fla) and (7). several functionally uncharacterized envelope proteins. Sequence and phylogenetic analyses led to the conclusion that, although many of the protein constituents are probably homologous, extensive sequence divergence during evolution clouds this homology so that a common ancestry can be established for all three types of systems for only two constituents, the ATPase and the TM protein. Sequence divergence of the individual T2S constituents has occurred at characteristic rates, apparently without shuffling of constituents between systems. The same is probably also true for the T4P and Fla systems. The family of ATPases is much larger than the family of TM proteins, and many ATPase homologues function in capacities unrelated to those considered here. Many phylogenetic clusters of the ATPases probably exhibit uniform function. Some of these have a corresponding TM protein homologue although others probably function without one. It is further shown that proteins that compose the different phylogenetic clusters in both the ATPase and the TM protein families exhibit unique structural characteristics that are of probable functional significance. The TM proteins are shown to have arisen by at least two dissimilar intragenic duplication events, one in the bacterial kingdom and one in the archaeal kingdom. The archaeal TM proteins are twice as large as the bacterial TM proteins, suggesting an oligomeric structure for the latter.

Adenosine Triphosphatases↗

PubMed2003

Two families of mechanosensitive channel proteins.

Mechanosensitive (MS) channels that provide protection against hypoosmotic shock are found in the membranes of organisms from the three domains of life: bacteria, archaea, and eucarya. Two families of ubiquitous MS channels are recognized, and these have been designated the MscL and MscS families. A high-resolution X-ray crystallographic structure is available for a member of the MscL family, and extensive molecular genetic, biophysical, and biochemical studies conducted in many laboratories have allowed postulation of a gating mechanism allowing the interconversion of a tightly closed state and an open state that controls transmembrane ion and metabolite fluxes. In contrast to the MscL channel proteins, which are of uniform topology, the much larger MscS family includes protein members with topologies that are predicted to vary from 3 to 11 alpha-helical transmembrane segments (TMSs) per polypeptide chain. Sequence analyses reveal that the three C-terminal TMSs of MscS channel proteins are conserved among family members and that the third of these three TMSs exhibits a 20-residue motif that is shared by the channel-forming TMS (TMS 1) of the MscL proteins. We propose that this C-terminal TMS in MscS family homologues serves as the channel-forming helix in a homooligomeric structure. The presence of a conserved residue pattern for the putative channel-forming TMSs in the MscL and MscS family proteins suggests a common structural organization, gating mechanism, and evolutionary origin.

Amino Acid Sequence↗

PubMed2002

Sequence and phylogenetic analyses of the twin-arginine targeting (Tat) protein export system.

Twin-arginine targeting (Tat) protein secretion systems consist of two protein types, members of the TatA and TatC families. Homologues of these proteins are found in many archaea, bacteria, chloroplasts and mitochondria. Every prokaryotic organism with a fully sequenced genome exhibits either neither family member, or between one and three paralogues of these two family members. The Arabidopsis thaliana genome encodes three of each. Although many mitochondrially encoded TatC homologues have been identified, corresponding TatA homologues have not been found in this organelle. Phylogenetic analyses reveal that most prokaryotic Tat systems consist of one TatC homologue and two sequence-divergent TatA homologues (TatA and TatB). When only one TatA homologue is present, TatB is missing, and when three TatA homologues are present, the third one arose by duplication of TatA, not TatB. Further, homologues most resembling TatB are more sequence-divergent than those more closely resembling TatA. In contrast to the TatA family, the TatC family shows phylogenetic clustering in strict accordance with organismal type. These results are discussed in terms of their probable structural, functional and evolutionary significance.

Arginine↗

PubMed2002

oriC region and replication termination site, dif, of the Xanthomonas campestris pv. campestris 17 chromosome.

A 13-kb DNA fragment containing oriC and the flanking genes thdF, orf900, yidC, rnpA, rpmH, oriC, dnaA, dnaN, recF, and gyrB was cloned from the gram-negative plant pathogen Xanthomonas campestris pv. campestris 17. These genes are conserved in order with other eubacterial oriC genes and code for proteins that share high degrees of identity with their homologues, except for orf900, which has a homologue only in Xylella fastidiosa. The dnaA/dnaN intergenic region (273 bp) identified to be the minimal oriC region responsible for autonomous replication has 10 pure AT clusters of four to seven bases and only three consensus DnaA boxes. These findings are in disagreement with the notion that typical oriCs contain four or more DnaA boxes located upstream of the dnaA gene. The X. campestris pv. campestris 17 attB site required for site-specific integration of cloned fragments from filamentous phage phiLf replicative form DNA was identified to be a dif site on the basis of similarities in nucleotide sequence and function with the Escherichia coli dif site required for chromosome dimer resolution and whose deletion causes filamentation of the cells. The oriC and dif sites were located at 12:00 and 6:00, respectively, on the circular X. campestris pv. campestris 17 chromosome map, similar to the locations found for E. coli sites. Computer searches revealed the presence of both the dif site and XerC/XerD recombinase homologues in 16 of the 42 fully sequenced eubacterial genomes, but eight of the dif sites are located far away from the 6:00 point instead of being placed opposite the cognate oriC. The differences in the relative position suggest that mechanisms different from that of E. coli may participate in the control of chromosome replication.

Amino Acid Sequence↗

PubMed2002

Export of L-isoleucine from Corynebacterium glutamicum: a two-gene-encoded member of a new translocator family.

Bacteria possess amino acid export systems, and Corynebacterium glutamicum excretes L-isoleucine in a process dependent on the proton motive force. In order to identify the system responsible for L-isoleucine export, we have used transposon mutagenesis to isolate mutants of C. glutamicum sensitive to the peptide isoleucyl-isoleucine. In one such mutant, strong peptide sensitivity resulted from insertion into a gene designated brnF encoding a hydrophobic protein predicted to possess seven transmembrane spanning helices. brnE is located downstream of brnF and encodes a second hydrophobic protein with four putative membrane-spanning helices. A mutant deleted of both genes no longer exports L-isoleucine, whereas an overexpressing strain exports this amino acid at an increased rate. BrnF and BrnE together are also required for the export of L-leucine and L-valine. BrnFE is thus a two-component export permease specific for aliphatic hydrophobic amino acids. Upstream of brnFE and transcribed divergently is an Lrp-like regulatory gene required for active export. Searches for homologues of BrnFE show that this type of exporter is widespread in prokaryotes but lacking in eukaryotes and that both gene products which together comprise the members of a novel family, the LIV-E family, generally map together within a single operon. Comparisons of the BrnF and BrnE phylogenetic trees show that gene duplication events in the early bacterial lineage gave rise to multiple paralogues that have been retained in alpha-proteobacteria but not in other prokaryotes analyzed.

Amino Acid Transport Systems↗

PubMedDate not supplied

The ubiquitous ThrE family of putative transmembrane amino acid efflux transporters.

We here report sequence analyses of a newly described family of putative amino acid exporters, the ThrE family. Homologues were identified in select bacteria, archaea and eukaryotes, but only in the fungal kingdom of eukaryotes. These proteins can exist either as single polypeptide chains or as pairs of polypeptide chains. Computational evidence suggests that these proteins exhibit 10 transmembrane alpha-helical segments (TMSs), having arisen from a five TMS precursor by an early intragenic duplication event. The phylogenetic tree of the ThrE family reveals that most proteins cluster according to organismal phylogeny with only a few exceptions, suggesting that the former proteins are orthologues. All family members exhibit hydrophilic N-terminal (and occasional C-terminal) extensions that show limited sequence similarity with a domain of unknown function found in many peptidases and proteases. The significance of these observations is discussed.

Amino Acid Sequence↗