Short cervix and vaginal progesterone: a model on how to tackle the problem of idiopathic preterm labor.

Preterm deliveries continue to be a major problem in obstetrics and pediatrics. Short cervical length has been identified as the most accurate way to predict preterm delivery. Recently, vaginally administered progesterone has been shown in separate studies to dramatically decrease the prematurity rate in patients with a short cervix. The research that came to this conclusion is a good model to be used to approach other etiologies of preterm labor and delivery.

Structure of the BamC two-domain protein obtained by Rosetta with a limited NMR data set.

The CS-RDC-NOE Rosetta program was used to generate the solution structure of a 27-kDa fragment of the Escherichia coli BamC protein from a limited set of NMR data. The BamC protein is a component of the essential five-protein ß-barrel assembly machine in E. coli. The first 100 residues in BamC were disordered in solution. The Rosetta calculations showed that BamC101₋344 forms two well-defined domains connected by an ~18-residue linker, where the relative orientation of the domains was not defined. Both domains adopt a helix-grip fold previously observed in the Bet v 1 superfamily. ¹5N relaxation data indicated a high degree of conformational flexibility for the linker connecting the N-terminal domain and the C-terminal domain in BamC. The results here show that CS-RDC-NOE Rosetta is robust and has a high tolerance for misassigned nuclear Overhauser effect restraints, greatly simplifying NMR structure determinations.

Crystal structure of BamD: an essential component of the ß-Barrel assembly machinery of gram-negative bacteria.

Folding and insertion of integral ß-barrel proteins in the outer membrane (OM) is an essential process for Gram-negative bacteria that requires the ß-barrel assembly machinery (BAM). Efficient OM protein (OMP) folding and insertion appears to require a consensus C-terminal signal in OMPs characterized by terminal F or W residues. The BAM complex is embedded in the OM and, in Escherichia coli, consists of the ß-barrel BamA and four lipoproteins BamBCDE. BamA and BamD are broadly distributed across all species of Gram-negative bacteria, whereas the other components are present in only a subset of species. BamA and BamD are also essential for viability, suggesting that these two proteins constitute the functional core of the bacterial BAM complex. Here, we present the crystal structure of BamD from the thermophilic bacteria Rhodothermus marinus refined to 2.15 Å resolution. The protein contains five tetratricopeptide repeats (TPRs) organized into two offset tandems, each capped by a terminal helix. The N-terminal domain contains three TPRs and displays remarkable structural similarity with proteins that recognize targeting signals in extended conformations. The C-terminal domain harbors the remaining two TPRs and previously described mutations that impair binding to other BAM components map to this domain. Therefore, the structure suggests a model where the C-terminal domain provides a scaffold for interaction with BAM components, while the N-terminal domain participates in interaction with the substrates, either recognizing the C-terminal consensus sequence or binding unfolded OMP intermediates.