The activation of human complement component C5 by a fluid phase C5 convertase.
Complement component C5 is converted to C5a and C5b by the cobra venom factor-dependent C3/C5 convertase CVF,Bb (EC 3.4.21.47). The C5 convertase produces selective proteolytic cleavage of an arginyl-leucine peptide bond at positions 74-75 in the alpha chain of C5. Circular dichroism studies in both the far and near UV regions provide evidence that a conformational change accompanies the C5 activation process. When C5 is activated by CVF,Bb in the presence of complement component C6, the C5b,6 complex is formed. However, when C6 is added after C5 has been converted to C5b, the C5b,6 complex fails to form. Therefore, the activation of C5 results in a transient binding site for C6. Hydrophobic sites are probably exposed upon C5 activation because C5b undergoes aggregation when C5 is converted to C5b in the absence of C6. Transmission electron micrographs of the C5 molecule indicate a multilobal, irregular ultrastructure with estimated dimensions of 104 X 140 X 168 A. Aggregated C5b has the appearance of globular particles with a diameter range of 350-700 A. Although C5 shares a number of features with the third component of complement, including a similar ultrastructure and partial sequence homology, C5 is devoid of the unusual thiol ester linkage found in C3. It is the labile thiol ester that permits covalent attachment between C3 and nucleophilic acceptors. In contrast, interactions between C5 and C6 or C5 and membranes remain noncovalent.
D000596:Amino Acids / Q000032:analysis; D002241:Carbohydrates / Q000032:analysis; D002852:Chromatography, Ion Exchange; D002942:Circular Dichroism; D003166:Complement Activating Enzymes / Q000378:metabolism*; D050577:Complement C3-C5 Convertases; D003182:Complement C5 / Q000032:analysis / Q000378:metabolism*; D015936:Complement C5a; D050776:Complement C5b; D006801:Humans; D008854:Microscopy, Electron
D000596:Amino Acids; D002241:Carbohydrates; D003182:Complement C5; D015936:Complement C5a; D050776:Complement C5b; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases