Functional and structural insight into properdin control of complement alternative pathway amplification

Properdin (FP) is an essential positive regulator of the complement alternative pathway (AP) providing stabilization of the C3 and C5 convertases, but its oligomeric nature challenges structural analysis. We describe here a novel FP deficiency (E244K) caused by a single point mutation which results in a very low level of AP activity. Recombinant FP E244K is monomeric, fails to support bacteriolysis, and binds weakly to C3 products. We compare this to a monomeric unit excised from oligomeric FP, which is also dysfunctional in bacteriolysis but binds the AP proconvertase, C3 convertase, C3 products and partially stabilizes the convertase. The crystal structure of such a FP-convertase complex suggests that the major contact between FP and the AP convertase is mediated by a single FP thrombospondin repeat and a small region in C3b. Small angle X-ray scattering indicates that FP E244K is trapped in a compact conformation preventing its oligomerization. Our studies demonstrate an essential role of FP oligomerization in vivo while our monomers enable detailed structural insight paving the way for novel modulators of complement.     

Interaction between initiator Met-tRNAfMet and elongation factor EF-Tu from E. coli

It has recently been shown that the non-formylated initiator Met-tRNAfMet from E. coli can form a stable ternary complex with the elongation factor EF-Tu and GTP. Using the protection of EF-Tu:GTP against spontaneous hydrolysis of the aminoacylester bond of Met-tRNAfMet, we confirm these results, and show that the protection is specific for the non-formylated form of the initiator tRNA. The ternary complex Met-tRNAfMet:EF-Tu:GTP can be isolated by column chromatography in a way similar to that demonstrated previously with EF-Tu complexed to the elongator Met-tRNAmMet. 32P-labeled Met-tRNAfMet within the ternary complex was analyzed by the footprinting technique. The pattern of initiator tRNA protection by EF-Tu against ribonuclease digestion is not significantly different from the one found previously for elongator tRNAs. These results lead us to suggest that the initiator tRNAfMet, under growth conditions which do not permit formylation, may to some extent function as an elongator tRNA.     

The blood vascular system in the head of the herring gull (Larus argentatus)

The structure and development of the blood vascular system in the head of the herring gull (Larus argentatus) have been studied using injection techniques and histological sections. Three different but interconnected divisions of the arterial system are recognized in the adult: the cerebral carotid artery system, the external ophthalmic artery system, and the external carotid artery system. Embryologically, the arterial system is characterized by changes in the relative development of these three divisions; the cerebral carotid system being the most prominent in the first half of the embryonic period. The venous system is divided into two parts, the rostral cephalic system and the caudal cephalic system, which drain separate regions of the head. The Rete ophthalmicum, which is an arteriovenous network associated with the external ophthalmic artery system, can be identified from the fifth day of incubation, and its development appears to be coupled with changes in the arterial supply to the eye. The possibility of a homology between the Rete ophthalmicum of birds and the Rete caroticum of mammals is briefly discussed.     

Blood Vessels in the Hind Limb of the Mallard (Anas platyrhynchos): Anatomical Evidence for a Sphincteric Action of Shunt Vessels in Connection with the Arterio-venous Heat Exchange System

Midtgård, U. 1980. Blood vessels in the hind limb of the Mallard (Anas platyrhynchos): anatomical evidence for a sphincteric action of shunt vessels in connection with the arterio-venous heat exchange system. (Institute of Comparative Anatomy, University of Copenhagen, Denmark.) — Acta zool. (Stockh.) 61(1): 39–49. The rete tibiotarsale is the main arterio-venous heat exchange system in the hind limb of the Mallard. A large arterial shunt and a venous shunt allow the blood to by-pass the rete. These shunt vessels must be able to constrict so as to direct the blood to the rete when heat conservation is needed. Using ordinary histological methods and the technique of Falck and Hillarp for demonstration of biogenic monoamines, it was shown that the arterial shunt is more muscular and receives a more dense adrenergic innervation than adjacent segments of the same vessel. Perfusion with noradrenaline before fixation revealed that the arterial shunt was able to reduce its lumen to near closure. No structure, in the ordinary sense of a sphincter, was found in the shunt vein but adrenergic nerves were scattered throughout the tunica media at the base of venous valves, suggesting that a sphincteric action at these sites is possible.