The location of the C8[gamma] binding site within the MACPF of C8[alpha] was suggested from a comparative analysis of MACPF sequences in C6, C7, C8[alpha], C8[beta], and C9.
Collectively, the results showed that binding between C8 and C9 is dependent on a site located within the C8[alpha] MACPF domain.
Results initially suggested a role for the N-terminal T1 module and MACPF domain but later studies using recombinant C8[beta] MACPF expressed in E.
Constructs that contained only the C8[beta] MACPF domain when combined with C8[alpha]-[gamma] were found to be hemolytically active, thus confirming that the C5b-7 binding site in C8[beta] lies within its MACPF domain (21).
The striking structural similarity between complement MACPF proteins and the CDCs suggests that complement uses a CDC-like mechanism for pore formation.
This is the first complete structure of a MAC family protein and of a protein containing two tightly associated MACPF domains.
The central part of the C8[alpha] and C8[beta] MACPF domains form large, four-stranded, antiparallel [beta]-sheets with a bend and twist in the middle, which gives them a "[GAMMA]" shape.