Simply Mycoplasma: The bacterium Mycoplasma pneumoniae , a human pathogen, has a genome of reduced size and is one of the simplest organisms that can reproduce outside of host cells. As such, it represents an excellent model organism in which to attempt a systems-level understanding of its biological organization. Now three papers provide a comprehensive and quantitative analysis of the proteome, the metabolic network, and the transcriptome of M. pneumoniae (see the Perspective by Ochman and Raghavan ). Anticipating what might be possible in the future for more complex organisms, Kühner et al. (p. 1235 ) combine analysis of protein interactions by mass spectrometry with extensive structural information on M. pneumoniae proteins to reveal how proteins work together as molecular machines and map their organization within the cell by electron tomography. The manageable genome size of M. pneumoniae allowed Yus et al. (p. 1263 ) to map the metabolic network of the organism manually and validate it experimentally. Analysis of the network aided development of a minimal medium in which the bacterium could be cultured. Finally, G‡ell et al. (p. 1268 ) applied state-of-the-art sequencing techniques to reveal that this “simple” organism makes extensive use of noncoding RNAs and has exon- and intron-like structure within transcriptional operons that allows complex gene regulation resembling that of eukaryotes.

Human and mouse cDNAs encoding a new β-1,3- N -acetylglucosaminyltransferase (β3GnT) have been isolated from fetal and newborn brain libraries. The human and mouse cDNAs included ORFs coding for predicted type II transmembrane polypeptides of 329 and 325 aa, respectively. The human and mouse β3GnT homologues shared 90% similarity. The β3GnT gene was widely expressed in human and mouse tissues, although differences in the transcript levels were visible, thus indicating possible tissue-specific regulation mechanisms. The β3GnT enzyme showed a marked preference for Gal(β1–4)Glc(NAc)-based acceptors, whereas no activity was detected on type 1 Gal(β1–3)GlcNAc and O-glycan core 1 Gal(β1–3)GalNAc acceptors. The new β3GnT enzyme was capable of both initiating and elongating poly- N -acetyllactosamine chains, which demonstrated its identity with the poly- N -acetyllactosamine synthase enzyme (E.C. 2.4.1.149), showed no similarity with the i antigen β3GnT enzyme described recently, and, strikingly, included several amino acid motifs in its protein that have been recently identified in β-1,3-galactosyltransferase enzymes. The comparison between the new UDP–GlcNAc:βGal β3GnT and the three UDP–Gal:βGlcNAc β-1,3-galactosyltransferases-I, -II, and -III reveals glycosyltransferases that share conserved sequence motifs though exhibiting inverted donor and acceptor specificities. This suggests that the conserved amino acid motifs likely represent residues required for the catalysis of the glycosidic (β1–3) linkage.

CD69 is involved in immune cell homeostasis, regulating the T cell-mediated immune response through the control of Th17 cell differentiation. However, natural ligands for CD69 have not yet been described. Using recombinant fusion proteins containing the extracellular domain of CD69, we have detected the presence of a ligand(s) for CD69 on human dendritic cells (DCs). Pulldown followed by mass spectrometry analyses of CD69-binding moieties on DCs identified galectin-1 as a CD69 counterreceptor. Surface plasmon resonance and anti-CD69 blocking analyses demonstrated a direct and specific interaction between CD69 and galectin-1 that was carbohydrate dependent. Functional assays with both human and mouse T cells demonstrated the role of CD69 in the negative effect of galectin-1 on Th17 differentiation. Our findings identify CD69 and galectin-1 to be a novel regulatory receptor-ligand pair that modulates Th17 effector cell differentiation and function.

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