The membrane attack complex (MAC) is an important i
nnate immune effector of the
complement terminal pathway that forms cytotoxic po
res on the surface of microbes. Despite
many years of research, MAC structure and mechanism
of action have remained elusive,
relying heavily on modelling and inference from bio
chemical experiments. Recent advances
in structural biology, specifically cryo electron m
icroscopy, have provided new insights into
the molecular mechanism of MAC assembly. Its unique
“split washer” shape, coupled with
an irregular giant β barrel architecture, enable an
atypical mechanism of hole punching and
represent a novel system for which to study pore fo
rmation. This review will introduce the
complement terminal pathway that leads to formation
of the MAC. Moreover, it will discuss
how structures of the pore and component proteins u
nderpin a mechanism for MAC function,
modulation and inhibition.