title: A common fold mediates vertebrate defense and bacterial attack.
abstract: Proteins containing membrane attack complex/perforin (MACPF) domains play important roles in vertebrate immunity, embryonic development, and neural-cell migration. In vertebrates, the ninth component of complement and perforin form oligomeric pores that lyse bacteria and kill virus-infected cells, respectively. However, the mechanism of MACPF function is unknown. We determined the crystal structure of a bacterial MACPF protein, Plu-MACPF from Photorhabdus luminescens, to 2.0 angstrom resolution. The MACPF domain reveals structural similarity with poreforming cholesterol-dependent cytolysins (CDCs) from Gram-positive bacteria. This suggests that lytic MACPF proteins may use a CDC-like mechanism to form pores and disrupt cell membranes. Sequence similarity between bacterial and vertebrate MACPF domains suggests that the fold of the CDCs, a family of proteins important for bacterial pathogenesis, is probably used by vertebrates for defense against infection.
authors: Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
authors: Carlos J
authors: CJ
authors: Rosado
authors: Ashley M
authors: AM
authors: Buckle
authors: Ruby H P
authors: RH
authors: Law
authors: Rebecca E
authors: RE
authors: Butcher
authors: Wan-Ting
authors: WT
authors: Kan
authors: Catherina H
authors: CH
authors: Bird
authors: Kheng
authors: K
authors: Ung
authors: Kylie A
authors: KA
authors: Browne
authors: Katherine
authors: K
authors: Baran
authors: Tanya A
authors: TA
authors: Bashtannyk-Puhalovich
authors: Noel G
authors: NG
authors: Faux
authors: Wilson
authors: W
authors: Wong
authors: Corrine J
authors: CJ
authors: Porter
authors: Robert N
authors: RN
authors: Pike
authors: Andrew M
authors: AM
authors: Ellisdon
authors: Mary C
authors: MC
authors: Pearce
authors: Stephen P
authors: SP
authors: Bottomley
authors: Jonas
authors: J
authors: Emsley
authors: A Ian
authors: AI
authors: Smith
authors: Jamie
authors: J
authors: Rossjohn
authors: Elizabeth L
authors: EL
authors: Hartland
authors: Ilia
authors: I
authors: Voskoboinik
authors: Joseph A
authors: JA
authors: Trapani
authors: Phillip I
authors: PI
authors: Bird
authors: Michelle A
authors: MA
authors: Dunstone
authors: James C
authors: JC
authors: Whisstock
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D054353:Perforin; D020637:Photorhabdus / Q000737:chemistry*; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014714:Vertebrates
chemical_list: D001426:Bacterial Proteins; D015938:Complement Membrane Attack Complex; D003603:Cytotoxins; C523178:MACPF protein, Photorhabdus luminescens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin