Structural basis for membrane attack complex inhibition by CD59
Abstract CD59 is an abundant immuno-regulatory receptor that protects human cells from damage during complement activation. Here we show how the receptor binds complement proteins C8 and C9 at the membrane to prevent insertion and polymerization of membrane attack complex (MAC) pores. We present cryoelectron microscopy structures of two
Couves EC +6 more
europepmc +6 more sources
The Membrane Attack Complex/Perforin Superfamily. [PDF]
The membrane attack complex/perforin (MACPF) superfamily consists of a diverse group of proteins involved in bacterial pathogenesis and sporulation as well as eukaryotic immunity, embryonic development, neural migration and fruiting body formation.
Moreno-Hagelsieb G +3 more
europepmc +6 more sources
Internalization of the Membrane Attack Complex Triggers NLRP3 Inflammasome Activation and IL-1β Secretion in Human Macrophages [PDF]
Interleukin 1β (IL-1β) plays a major role in inflammation and is secreted by immune cells, such as macrophages, upon recognition of danger signals. Its secretion is regulated by the inflammasome, the assembly of which results in caspase 1 activation ...
Ines Diaz-del-Olmo +8 more
doaj +2 more sources
Structural basis of complement membrane attack complex formation
The membrane attack complex (MAC) is an immune effector that kills pathogens by forming pores in their membrane. Here the authors use cryo-electron microscopy to reveal that the full MAC is an asymmetric pore with a split-washer configuration and ...
Marina Serna +3 more
doaj +4 more sources
Bactericidal membrane attack complex formation initiates at the new pole of E. coli [PDF]
Human immune protection against bacteria critically depends on activation of the complement system. The direct bacteriolytic activity of complement molecules against Gram-negative bacteria acts via the formation of Membrane Attack Complex (MAC) pores ...
Marije F L van ‘t Wout +7 more
doaj +2 more sources
Design of miniprotein inhibitors targeting complement C9 to block membrane attack complex assembly [PDF]
The abnormal formation of the membrane attack complex (MAC) is intrinsically linked to a range of acute and chronic immune diseases. The insertion of complement C9 into the membrane is the final step and kinetic bottleneck of MAC formation.
Min Li +16 more
doaj +2 more sources
Single-molecule kinetics of pore assembly by the membrane attack complex [PDF]
The membrane attack complex (MAC) is a hetero-oligomeric protein assembly that kills pathogens by perforating their cell envelopes. Here, the authors use atomic force microscopy to show that MAC proteins oligomerize within the membrane, allowing them to ...
Edward S. Parsons +11 more
doaj +2 more sources
CD59 Protects Primary Human Cerebrovascular Smooth Muscle Cells from Cytolytic Membrane Attack Complex [PDF]
Cerebral amyloid angiopathy is characterized by a weakening of the small- and medium-sized cerebral arteries, as their smooth muscle cells are progressively replaced with acellular amyloid β, increasing vessel fragility and vulnerability to ...
Carson D. Whinnery +4 more
doaj +2 more sources
CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers [PDF]
The complement membrane attack complex (MAC) is a lytic immune pore that kills pathogens. Here the authors use cryoEM to provide a structural and biophysical mechanism for how β-pore forming proteins breach the lipid bilayer, providing pathways to ...
Anaïs Menny +8 more
doaj +2 more sources
Outer membrane permeabilization by the membrane attack complex sensitizes Gram-negative bacteria to antimicrobial proteins in serum and phagocytes. [PDF]
Infections with Gram-negative bacteria form an increasing risk for human health due to antibiotic resistance. Our immune system contains various antimicrobial proteins that can degrade the bacterial cell envelope.
Dani A C Heesterbeek +7 more
doaj +2 more sources

