MACPF
MAC/Perforin domain | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | MACPF | ||||||||
TCDB | 1.C.39 | ||||||||
OPM superfamily | 168 | ||||||||
OPM protein | 6h04 | ||||||||
Membranome | 233 | ||||||||
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The Membrane Attack Complex/Perforin (MACPF)
Archetypal members of the family are
Families
As of early 2016, there are three families belonging to the MACPF superfamily:
- 1.C.12 - The Thiol-activated Cholesterol-dependent Cytolysin (CDC) Family
- 1.C.39 - The Membrane Attack Complex/Perforin (MACPF) Family
- 1.C.97 - The Pleurotolysin Pore-forming (Pleurotolysin) Family
Membrane Attack Complex/Perforin (MACPF) Family
Proteins containing MACPF domains play key roles in vertebrate immunity, embryonic development, and neural-cell migration.[10] The ninth component of complement and perforin form oligomeric pores that lyse bacteria and kill virus-infected cells, respectively. The crystal structure of a bacterial MACPF protein, Plu-MACPF from Photorhabdus luminescens was determined (PDB: 2QP2).[11] The MACPF domain is structurally similar to pore-forming cholesterol-dependent cytolysins from gram-positive bacteria, suggesting that MACPF proteins create pores and disrupt cell membranes similar to cytolysin. A representative list of proteins belonging to the MACPF family can be found in the Transporter Classification Database.
Biological roles of MACPF domain containing proteins
Many proteins belonging to the MACPF superfamily play key roles in plant and animal immunity.
Complement proteins C6-C9 all contain a MACPF domain and assemble into the membrane attack complex. C6, C7 and C8β appear to be non-lytic and function as scaffold proteins within the MAC. In contrast both C8α and C9 are capable of lysing cells. The final stage of MAC formation involves polymerisation of C9 into a large pore that punches a hole in the outer membrane of gram-negative bacteria.
The plant protein CAD1 (TC# 1.C.39.11.3) functions in the plant immune response to bacterial infection.[13][14]
The sea anemone Actineria villosa uses a MACPF (AvTX-60A; TC# 1.C.39.10.1)protein as a lethal toxin.[15]
MACPF proteins are also important for the invasion of the
Not all MACPF proteins function in defence or attack. For example,
Functionally uncharacterised MACPF proteins are sporadically distributed in bacteria. Several species of Chlamydia contain MACPF proteins.[21] The insect pathogenic bacteria Photorhabdus luminescens also contains a MACPF protein, however, this molecule appears non-lytic.[8]
Structure and mechanism
The X-ray crystal structure of Plu-MACPF, a protein from the
It is suggested that MACPF proteins and CDCs form pores in the same way (figure 1). Like CDC's MACPF proteins are thus β-pore forming toxins that act like a molecular hole punch.
Other crystal structures for members of the MACPF superfamily can be found in RCSB: i.e., 3KK7, 3QOS, 3QQH, 3RD7, 3OJY
Control of MACPF proteins
Complement regulatory proteins such as
Other proteins that bind to the MAC include C8γ. This protein belongs to the lipocalin family and interacts with C8α. The binding site on C8α is known, however, the precise role of C8γ in the MAC remains to be understood.[26][27]
Role in human disease
Deficiency of C9, or other components of the MAC results in an increased susceptibility to diseases caused by
The MACPF protein DBCCR1 may function as a tumor suppressor in bladder cancer.[3][32]
Human proteins containing this domain
C6; C7; C8A; C8B; C9; FAM5B; FAM5C; MPEG1;
References
- S2CID 17084919.
- PMID 1722985.
- ^ PMID 18564372.
- S2CID 4330219.
- ^ S2CID 39504110.
- ^ PMID 17475905.
- S2CID 22684521.
- ^ S2CID 20372720.
- S2CID 44959101.
- PMID 18778941.
- S2CID 20372720.
- PMID 17116752.
- PMID 15799997.
- S2CID 37799485.
- PMID 15019483.
- PMID 15520375.
- S2CID 19341572.
- S2CID 206576029.
- PMID 10373306.
- S2CID 4274979.
- S2CID 7748405.
- S2CID 8345038.
- S2CID 1613454.
- PMID 16844690.
- PMID 7544344.
- S2CID 86614986.
- ^ PMID 17692377.
- PMID 7512825.
- S2CID 3227108.
- PMID 11287977.
- S2CID 30781596.
- S2CID 3620390.