C3, KEY COMPONENT OF THE COMPLEMENT SYSTEM INVOLVED IN NON SPECIFIC PATHOGEN RECOGNITION

SILVA W. D.(1)

(1)Laboratório de Biologia do Reconhecer, CBB, UENF

The complement system is one of the first lines of innate defense against pathogenic microorganisms. Its activation leads to the formation of inflammatory peptides, opsonic fragments, and the membrane attack protein. C3 contains an internal thioester bond which is formed by the association of the sulfhydryl group (Cys 1010) and a glutamyl carbonyl (Gln 1012) on the C3 -chain. Proteolytic cleavage of a 77 – residue peptide from the N-terminus of the C3 -chain generates C3a and C3b. Attachment of C3b is accomplished through a covalent link between the carbonyl group of the metastable thioester and either –NH2 or –OH groups of proteins or carbohydrate structures exposed on the pathogen cell surface. C3 molecules that do not bind in this way are inactivated by binding to water molecules. Covalent binding of C3 tags invading pathogens as foreign substances addressing them to be phagocytosed or lysed. C3, once it is deposited covalently as C3b on the pathogen cell surface it can be directed to either an amplification or inactivation step. Amplification requires intervention of factor B, a serine pro-enzyme, which is activated by factor D forming the C3 convertase C3bBb. Inactivation requires intervention of four distinct proteins, factor I, factor H, complement receptor type 1 (CD35) and the membrane cofactor protein (CD46), which by acting in concert cleave C3b into an inactive product, iC3b, releasing a small peptide, C3f. On host cell surfaces bearing polyanions such as sialic acid, factor H binds to C3b with a higher affinity than does factor B. On microbial surfaces that lack a polyanionic coating, factor B binds to C3b with a higher affinity than does factor H, leading to amplified cleavage of C3. Amplification leads to destruction of pathogens while inactivation allows pathogens multiplication.

CORRESPONDENCE TO:

Wilmar Dias da Silva, Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campo dos Goytacazes, RJ, Av. Alberto Lamengo, nº 2000. Fone: (22) 2726 1422. Email: wds@uenf.br