Structural basis of gating by the outer membrane transporter FecA

Siderophore-mediated acquisition systems facilitate iron uptake. We present the crystallographic structure of the integral outer membrane receptor FecA from Escherichia coli with and without ferric citrate at 2.5 and 2.0 angstrom resolution. FecA is composed of three distinct domains: the barrel, plug, and NH2-terminal extension. Binding of ferric citrate triggers a conformational change of the extracellular loops that close the external pocket of FecA. Ligand-induced allosteric transitions are propagated through the outer membrane by the plug domain, signaling the occupancy of the receptor in the periplasm. These data establish the structural basis of gating for receptors dependent on the cytoplasmic membrane protein TonB. By compiling available data for this family of receptors, we propose a mechanism for the energy-dependent transport of siderophores.     

Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA

The SecA adenosine triphosphatase (ATPase) mediates extrusion of the amino termini of secreted proteins from the eubacterial cytosol based on cycles of reversible binding to the SecYEG translocon. We have determined the crystal structure of SecA with and without magnesium-adenosine diphosphate bound to the high-affinity ATPase site at 3.0 and 2.7 angstrom resolution, respectively. Candidate sites for preprotein binding are located on a surface containing the SecA epitopes exposed to the periplasm upon binding to SecYEG and are thus positioned to deliver preprotein to SecYEG. Comparisons with structurally related ATPases, including superfamily I and II ATP-dependent helicases, suggest that the interaction geometry of the tandem motor domains in SecA is modulated by nucleotide binding, which is shown by fluorescence anisotropy experiments to reverse an endothermic domain-dissociation reaction hypothesized to gate binding to SecYEG.     

Relationship between biochemical markers and radiographic scores in the evaluation of the osteoarticular status of Warmblood stallions

Establishing the osteoarticular status of the horse is often performed by means of radiological screening of the animals. Widespread blood sampling could reveal to be an interesting alternative to this procedure which is time consuming and sometimes technically difficult. The aim of this study was to investigate the relationship between the radiological status of the horses and the levels of biochemical markers of cartilage degradation and synovial inflammation. A specific radiological scoring and classification system was therefore developed and applied on 63 stallions presented for studbook admission. Additionally, groups of horses were established according to the occurrence of osteochondrosis, degenerative joint disease and distal interphalangeal joint effusion. Insulin growth factor-I, myeloperoxidases, Coll2-1 and Coll2-1NO₂ were used as blood markers. The combination of the blood parameters did not seem to correlate with the used scoring system. Coll2-1NO₂ levels however tended to increase with poorer radiological class and this could therefore potentially be a useful predictor of the osteoarticular status in the horse. Coll2-1 levels were significantly higher in the degenerative joint disease group. A high percentage of horses with distal interphalangeal joint effusion was present in this study and was associated with decreased IGF-I and increased Coll2-1 levels.     

Small intestinal intussusception in five dogs with acute renal failure and suspected leptospirosis (L. australis)

Objectives – This case series describes 5 dogs with small intestinal intussusception and acute kidney injury due to infection with Leptospira interrogans serovar Australis.
Case Series Summary – Small intestinal intussusception was observed in 4 dogs diagnosed with acute kidney injury due to leptospirosis presented between 1997 and 2005. Intussusception was diagnosed at initial presentation or later during hospitalization. An additional dog fulfilling our inclusion criteria was presented to a small animal specialty clinic nearby and was included. Upon admission, all dogs were severely azotemic and thrombocytopenic. All 5 dogs showed the strongest microscopic agglutination test serology reaction to L. interrogans serovar Australis. Two dogs survived with no apparent residual renal damage, 1 survived with subsequent mild chronic kidney disease, and 2 dogs were euthanized at the owners' request due to a guarded prognosis.
New or Unique Information Provided – Intussusception can occur or may be seen in dogs with leptospirosis due to L. interrogans serovar Australis and patients should be monitored closely for this potential complication. As all 5 dogs described in this case series showed the highest titer for L. interrogans serovar Australis, these precautions may be especially applied in geographic areas where this particular serovar is seen.