PDBsum entry 2qp2

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protein metals links
Unknown function PDB id
Protein chain
498 a.a. *
_CA ×2
Waters ×356
* Residue conservation analysis
PDB id:
Name: Unknown function
Title: Structure of a macpf/perforin-like protein
Structure: Unknown protein. Chain: a. Engineered: yes
Source: Photorhabdus luminescens subsp. Laumon organism_taxid: 141679. Strain: subsp. Laumondii. Gene: photorhabdus luminescens. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.00Å     R-factor:   0.182     R-free:   0.204
Authors: C.J.Rosado,A.M.Buckle,R.H.P.Law,R.E.Butcher,W.T.Kan,C.H.Bird K.A.Browne,K.Baran,T.A.Bashtannyk-Puhalovich,N.G.Faux,W.Won C.J.Porter,R.N.Pike,A.M.Ellisdon,M.C.Pearce,S.P.Bottomley,J A.I.Smith,J.Rossjohn,E.L.Hartland,I.Voskoboinik,J.A.Trapani P.I.Bird,M.A.Dunstone,J.C.Whisstock
Key ref:
C.J.Rosado et al. (2007). A common fold mediates vertebrate defense and bacterial attack. Science, 317, 1548-1551. PubMed id: 17717151 DOI: 10.1126/science.1144706
22-Jul-07     Release date:   04-Sep-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q7N6X0  (Q7N6X0_PHOLL) -  Complete genome; segment 5/17
510 a.a.
498 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     metal ion binding     1 term  


DOI no: 10.1126/science.1144706 Science 317:1548-1551 (2007)
PubMed id: 17717151  
A common fold mediates vertebrate defense and bacterial attack.
C.J.Rosado, A.M.Buckle, R.H.Law, R.E.Butcher, W.T.Kan, C.H.Bird, K.Ung, K.A.Browne, K.Baran, T.A.Bashtannyk-Puhalovich, N.G.Faux, W.Wong, C.J.Porter, R.N.Pike, A.M.Ellisdon, M.C.Pearce, S.P.Bottomley, J.Emsley, A.I.Smith, J.Rossjohn, E.L.Hartland, I.Voskoboinik, J.A.Trapani, P.I.Bird, M.A.Dunstone, J.C.Whisstock.
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.
  Selected figure(s)  
Figure 1.
Fig. 1. The structure of Plu-MACPF. (A) Secondary-structure elements are labeled (see also fig. S2); CH1 and CH2 are shown in red. Two Ca atoms are shown as gray spheres, and the numbers represent the strand numbering of the B sheet. (B) Structure of PFO (19). Core elements of secondary structure common to both MACPF and CDCs are colored accordingly. In PFO, the region equivalent to the C sheet in MACPF is continuous with the light blue sheet and is shown in yellow. The first strand of the light blue sheet is shortened and at the top of the sheet, and the region in PFO equivalent to the A sheet (magenta) has collapsed over to form ß-sheet hydrogen bonding with the second strand of the light blue sheet. (C) Stereo view of the superposition of the core of MACPF and PFO.
Figure 4.
Fig. 4. Position of disease-linked mutations in perforin. The positions of mutations in perforin that cause early onset FHL (yellow) and late onset atypical FHL (pale green) are shown by spheres (table S2). The numbering is for perforin, and red text indicates a mutation of a conserved residue (table S2). The positions of G149 and E261 in perforin are approximate, because these are insertions relative to Plu-MACPF. The position of the CD59 binding site in C9 and C8 is indicated by a black circle (30).
  The above figures are reprinted by permission from the AAAs: Science (2007, 317, 1548-1551) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21368207 C.J.Gobler, D.L.Berry, S.T.Dyhrman, S.W.Wilhelm, A.Salamov, A.V.Lobanov, Y.Zhang, J.L.Collier, L.L.Wurch, A.B.Kustka, B.D.Dill, M.Shah, N.C.VerBerkmoes, A.Kuo, A.Terry, J.Pangilinan, E.A.Lindquist, S.Lucas, I.T.Paulsen, T.K.Hattenrath-Lehmann, S.C.Talmage, E.A.Walker, F.Koch, A.M.Burson, M.A.Marcoval, Y.Z.Tang, G.R.Lecleir, K.J.Coyne, G.M.Berg, E.M.Bertrand, M.A.Saito, V.N.Gladyshev, and I.V.Grigoriev (2011).
Niche of harmful alga Aureococcus anophagefferens revealed through ecogenomics.
  Proc Natl Acad Sci U S A, 108, 4352-4357.  
20075937 A.J.Brennan, J.Chia, J.A.Trapani, and I.Voskoboinik (2010).
Perforin deficiency and susceptibility to cancer.
  Cell Death Differ, 17, 607-615.  
  20539776 B.F.Kafsack, and V.B.Carruthers (2010).
Apicomplexan perforin-like proteins.
  Commun Integr Biol, 3, 18-23.  
  20100082 F.Zhou (2010).
Perforin: more than just a pore-forming protein.
  Int Rev Immunol, 29, 56-76.  
20634814 Saint Basile, G.Ménasché, and A.Fischer (2010).
Molecular mechanisms of biogenesis and exocytosis of cytotoxic granules.
  Nat Rev Immunol, 10, 568-579.  
  20536557 J.Lieberman (2010).
Granzyme A activates another way to die.
  Immunol Rev, 235, 93.  
20532941 J.Tanaka, T.Nakae, T.Onoe, Y.Horiuchi, H.Miyamoto, J.Adan-Kubo, H.Adachi, and Y.Ono (2010).
Complement-mediated bacteriolysis after binding of specific antibodies to drug-resistant Pseudomonas aeruginosa: morphological changes observed by using a field emission scanning electron microscope.
  J Infect Chemother, 16, 383-387.  
20351143 L.D.Taylor, D.E.Nelson, D.W.Dorward, W.M.Whitmire, and H.D.Caldwell (2010).
Biological characterization of Chlamydia trachomatis plasticity zone MACPF domain family protein CT153.
  Infect Immun, 78, 2691-2699.  
20457744 L.Holm, and P.Rosenström (2010).
Dali server: conservation mapping in 3D.
  Nucleic Acids Res, 38, W545-W549.  
  20944225 Q.Xu, P.Abdubek, T.Astakhova, H.L.Axelrod, C.Bakolitsa, X.Cai, D.Carlton, C.Chen, H.J.Chiu, T.Clayton, D.Das, M.C.Deller, L.Duan, K.Ellrott, C.L.Farr, J.Feuerhelm, J.C.Grant, A.Grzechnik, G.W.Han, L.Jaroszewski, K.K.Jin, H.E.Klock, M.W.Knuth, P.Kozbial, S.S.Krishna, A.Kumar, W.W.Lam, D.Marciano, M.D.Miller, A.T.Morse, E.Nigoghossian, A.Nopakun, L.Okach, C.Puckett, R.Reyes, H.J.Tien, C.B.Trame, H.van den Bedem, D.Weekes, T.Wooten, A.Yeh, J.Zhou, K.O.Hodgson, J.Wooley, M.A.Elsliger, A.M.Deacon, A.Godzik, S.A.Lesley, and I.A.Wilson (2010).
Structure of a membrane-attack complex/perforin (MACPF) family protein from the human gut symbiont Bacteroides thetaiotaomicron.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 1297-1305.
PDB code: 3kk7
20448139 Souza, and L.Aravind (2010).
UMA and MABP domains throw light on receptor endocytosis and selection of endosomal cargoes.
  Bioinformatics, 26, 1477-1480.  
21037563 R.H.Law, N.Lukoyanova, I.Voskoboinik, T.T.Caradoc-Davies, K.Baran, M.A.Dunstone, M.E.D'Angelo, E.V.Orlova, F.Coulibaly, S.Verschoor, K.A.Browne, A.Ciccone, M.J.Kuiper, P.I.Bird, J.A.Trapani, H.R.Saibil, and J.C.Whisstock (2010).
The structural basis for membrane binding and pore formation by lymphocyte perforin.
  Nature, 468, 447-451.
PDB code: 3nsj
20860583 S.C.Kondos, T.Hatfaludi, I.Voskoboinik, J.A.Trapani, R.H.Law, J.C.Whisstock, and M.A.Dunstone (2010).
The structure and function of mammalian membrane-attack complex/perforin-like proteins.
  Tissue Antigens, 76, 341-351.  
20497254 S.Konjar, V.R.Sutton, S.Hoves, U.Repnik, H.Yagita, T.Reinheckel, C.Peters, V.Turk, B.Turk, J.A.Trapani, and N.Kopitar-Jerala (2010).
Human and mouse perforin are processed in part through cleavage by the lysosomal cysteine proteinase cathepsin L.
  Immunology, 131, 257-267.  
20017192 S.M.Black, M.E.Schott, B.H.Batdorf, B.A.Benson, M.S.Rutherford, B.K.Levay-Young, and A.P.Dalmasso (2010).
IL-4 induces protection of vascular endothelial cells against killing by complement and melittin through lipid biosynthesis.
  Eur J Immunol, 40, 803-812.  
20731542 V.R.Sutton, and J.A.Trapani (2010).
Proteases in lymphocyte killer function: redundancy, polymorphism and questions remaining.
  Biol Chem, 391, 873-879.  
19095897 B.F.Kafsack, J.D.Pena, I.Coppens, S.Ravindran, J.C.Boothroyd, and V.B.Carruthers (2009).
Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells.
  Science, 323, 530-533.  
19487666 J.Chia, K.P.Yeo, J.C.Whisstock, M.A.Dunstone, J.A.Trapani, and I.Voskoboinik (2009).
Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancer.
  Proc Natl Acad Sci U S A, 106, 9809-9814.  
19292457 J.J.Flanagan, R.K.Tweten, A.E.Johnson, and A.P.Heuck (2009).
Cholesterol exposure at the membrane surface is necessary and sufficient to trigger perfringolysin O binding.
  Biochemistry, 48, 3977-3987.  
19442503 M.Bischofberger, M.R.Gonzalez, and F.G.van der Goot (2009).
Membrane injury by pore-forming proteins.
  Curr Opin Cell Biol, 21, 589-595.  
19614666 M.S.Roiko, and V.B.Carruthers (2009).
New roles for perforins and proteases in apicomplexan egress.
  Cell Microbiol, 11, 1444-1452.  
19098006 R.Kayed, A.Pensalfini, L.Margol, Y.Sokolov, F.Sarsoza, E.Head, J.Hall, and C.Glabe (2009).
Annular protofibrils are a structurally and functionally distinct type of amyloid oligomer.
  J Biol Chem, 284, 4230-4237.  
19307185 R.W.Bourdeau, E.Malito, A.Chenal, B.L.Bishop, M.W.Musch, M.L.Villereal, E.B.Chang, E.M.Mosser, R.F.Rest, and W.J.Tang (2009).
Cellular functions and X-ray structure of anthrolysin O, a cholesterol-dependent cytolysin secreted by Bacillus anthracis.
  J Biol Chem, 284, 14645-14656.
PDB code: 3cqf
18175768 A.S.Konagurthu, P.J.Stuckey, and A.M.Lesk (2008).
Structural search and retrieval using a tableau representation of protein folding patterns.
  Bioinformatics, 24, 645-651.  
18564372 C.J.Rosado, S.Kondos, T.E.Bull, M.J.Kuiper, R.H.Law, A.M.Buckle, I.Voskoboinik, P.I.Bird, J.A.Trapani, J.C.Whisstock, and M.A.Dunstone (2008).
The MACPF/CDC family of pore-forming toxins.
  Cell Microbiol, 10, 1765-1774.  
18440555 D.J.Slade, L.L.Lovelace, M.Chruszcz, W.Minor, L.Lebioda, and J.M.Sodetz (2008).
Crystal structure of the MACPF domain of human complement protein C8 alpha in complex with the C8 gamma subunit.
  J Mol Biol, 379, 331-342.
PDB code: 2rd7
18502634 E.Ikonen, and M.Jansen (2008).
Cellular sterol trafficking and metabolism: spotlight on structure.
  Curr Opin Cell Biol, 20, 371-377.  
18772390 F.C.Kurschus, E.Fellows, E.Stegmann, and D.E.Jenne (2008).
Granzyme B delivery via perforin is restricted by size, but not by heparan sulfate-dependent endocytosis.
  Proc Natl Acad Sci U S A, 105, 13799-13804.  
18778941 G.Anderluh, and J.H.Lakey (2008).
Disparate proteins use similar architectures to damage membranes.
  Trends Biochem Sci, 33, 482-490.  
  18606691 J.A.Carrero, H.Vivanco-Cid, and E.R.Unanue (2008).
Granzymes drive a rapid listeriolysin O-induced T cell apoptosis.
  J Immunol, 181, 1365-1374.  
18390664 S.E.Gelber, J.L.Aguilar, K.L.Lewis, and A.J.Ratner (2008).
Functional and phylogenetic characterization of Vaginolysin, the human-specific cytolysin from Gardnerella vaginalis.
  J Bacteriol, 190, 3896-3903.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.