On the basis of comparative studies of known antibody structures and sequences it has been argued that there is a small repertoire of main-chain conformations for at least five of the six hypervariable regions of antibodies, and that the particular conformation adopted is determined by a few key conserved residues. These hypotheses are now supported by reasonably successful predictions of the structures of most hypervariable regions of various antibodies, as revealed by comparison with their subsequently determined structures.

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Contractile tails are composed of an inner tube wrapped by an outer sheath assembled in an extended, metastable conformation that stores mechanical energy necessary for its contraction. Contraction is used to propel the rigid inner tube towards target cells for DNA or toxin delivery. Although recent studies have revealed the structure of the contractile sheath of the type VI secretion system, the mechanisms by which its polymerization is controlled and coordinated with the assembly of the inner tube remain unknown. Here we show that the starfish-like TssA dodecameric complex interacts with tube and sheath components. Fluorescence microscopy experiments in enteroaggregative Escherichia coli reveal that TssA binds first to the type VI secretion system membrane core complex and then initiates tail polymerization. TssA remains at the tip of the growing structure and incorporates new tube and sheath blocks. On the basis of these results, we propose that TssA primes and coordinates tail tube and sheath biogenesis.

Phages of the Caudovirales order possess a tail that recognizes the host and ensures genome delivery upon infection. The X-ray structure of the approximately 1.8 MDa host adsorption device (baseplate) from the lactococcal phage TP901-1 shows that the receptor-binding proteins are pointing in the direction of the host, suggesting that this organelle is in a conformation ready for host adhesion. This result is in marked contrast with the lactococcal phage p2 situation, whose baseplate is known to undergo huge conformational changes in the presence of Ca 2þ to reach its active state. In vivo infection experiments confirmed these structural observations by demonstrating that Ca 2þ ions are required for host adhesion among p2-like phages (936-species) but have no influence on TP901-1-like phages (P335-species). These data suggest that these two families rely on diverse adhesion strategies which may lead to different signaling for genome release.bacteriophage | crystal structure | Lactococcus lactis | siphoviridae | viral infection B acterial viruses (phages) are elegant nanomachines infecting their hosts with high specificity and efficiency. The vast majority of them belong to the Caudovirales order and possess a tail appendage used to recognize the host and ensure genome delivery. This organelle seems to be responsible for the unequaled efficacy of these virions, as compared to eukaryotic viruses, as each phage particle can infect a target cell (1). The initial events of the infection process have been characterized for a limited number of phages demonstrating that dramatic conformational changes at the distal tail end accompany the DNA injection event (2-7). Binding of myophage T4 to the host lipopolysaccharides induces dramatic rearrangements of its tail extremity allowing irreversible commitment to the target cell followed by puncturing of its surface (3, 5). The emerging picture for Podoviridae is that after attachment to the cell envelope, the minor phage proteins are ejected to form a tube across the periplasm thereby directing the viral DNA into the host cytoplasm (8). Siphophage p2, belonging to the 936-species of lactococcal phages, exhibits a Ca 2þ -mediated activation mechanism inducing a 200°rotation of the receptor-binding proteins (RBPs) to establish multiple interactions with host saccharides and initiate infection (7). Here we report the crystal structure of the baseplate from the lactoccocal phage TP901-1 (P335-species) at 3.8 Å resolution and show that it is in a conformation ready for host adhesion, ruling out the involvement of a Ca 2þ -mediated or any other major conformational changes of this organelle at this initial step. We extended these conclusions by demonstrating that authentic virions can infect their host with maximal efficacy in the absence of added Ca 2þ and that this behavior is conserved among the TP901-1 phage species (P335). We therefore suggest that TP901-1-like phages do not rely on baseplate conformational changes for host adsorption, in contrast to what has been observed for ...

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In mammals, odorant binding proteins may play an important role in the transport of odors towards specific olfactory receptors on sensory neurones across the aqueous compartment of the nasal mucus. We have solved the X-ray structure of such a transport protein, bovine odorant binding protein (OBP) at 2.0 A resolution. The beta-barrel of OBP is similar to that of lipocalins, but OBP dimer association results from domain swapping, an observation unique among the lipocalins. The alpha-helix of each monomer stacks against the beta-barrel of the other monomer. Contrary to previous reports, each monomer has an internal buried cavity which could accommodate a naturally occurring molecule. Besides this cavity, an open cavity is located at the dimer interface. Data in solution suggest that this central cavity may be a binding site created by domain swapping.

Lactococcus lactis is a Gram-positive bacterium used extensively by the dairy industry for the manufacture of fermented milk products. The double-stranded DNA bacteriophage p2 infects specific L. lactis strains using a receptor-binding protein (RBP) located at the tip of its noncontractile tail. We have solved the crystal structure of phage p2 RBP, a homotrimeric protein composed of three domains: the shoulders, a beta-sandwich attached to the phage; the neck, an interlaced beta-prism; and the receptor-recognition head, a seven-stranded beta-barrel. We used the complex of RBP with a neutralizing llama VHH domain to identify the receptor-binding site. Structural similarity between the recognition-head domain of phage p2 and those of adenoviruses and reoviruses, which invade mammalian cells, suggests that these viruses, despite evolutionary distant targets, lack of sequence similarity and the different chemical nature of their genomes (DNA versus RNA), might have a common ancestral gene.