A common fold mediates vertebrate defense and bacterial attack.
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.
Rosado
Carlos J
CJ
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Buckle
Ashley M
AM
Law
Ruby H P
RH
Butcher
Rebecca E
RE
Kan
Wan-Ting
WT
Bird
Catherina H
CH
Ung
Kheng
K
Browne
Kylie A
KA
Baran
Katherine
K
Bashtannyk-Puhalovich
Tanya A
TA
Faux
Noel G
NG
Wong
Wilson
W
Porter
Corrine J
CJ
Pike
Robert N
RN
Ellisdon
Andrew M
AM
Pearce
Mary C
MC
Bottomley
Stephen P
SP
Emsley
Jonas
J
Smith
A Ian
AI
Rossjohn
Jamie
J
Hartland
Elizabeth L
EL
Voskoboinik
Ilia
I
Trapani
Joseph A
JA
Bird
Phillip I
PI
Dunstone
Michelle A
MA
Whisstock
James C
JC
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
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