Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Stabilizing Isopeptide Bonds Revealed in Gram-Positive Bacterial Pilus Structure
Hae Joo Kang,1,2Fasséli Coulibaly,1,2Fiona Clow,1,3Thomas Proft,1,3*Edward N. Baker1,2*
Many bacterial pathogens have long, slender pili through whichthey adhere to host cells. The crystal structure of the majorpilin subunit from the Gram-positive human pathogen Streptococcuspyogenes at 2.2 angstroms resolution reveals an extended structurecomprising two all-β domains. The molecules associate incolumns through the crystal, with each carboxyl terminus adjacentto a conserved lysine of the next molecule. This lysine formsthe isopeptide bonds that link the subunits in native pili,validating the relevance of the crystal assembly. Each subunitcontains two lysine-asparagine isopeptide bonds generated byan intramolecular reaction, and we find evidence for similarisopeptide bonds in other cell surface proteins of Gram-positivebacteria. The present structure explains the strength and stabilityof such Gram-positive pili and could facilitate vaccine development.
1 Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1010, New Zealand. 2 School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand. 3 School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
* To whom correspondence should be addressed. E-mail: ted.baker{at}auckland.ac.nz (E.N.B.); t.proft{at}auckland.ac.nz (T.P.)
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Todd O. Yeates and Robert T. Clubb (7 December 2007) Science318 (5856), 1558.
[DOI: 10.1126/science.1151398] |Summary »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Collagen-Binding Adhesin, Acb, and Ten Other Putative MSCRAMM and Pilus Family Proteins of Streptococcus gallolyticus subsp. gallolyticus (Streptococcus bovis Group, Biotype I).
J. Sillanpaa, S. R. Nallapareddy, X. Qin, K. V. Singh, D. M. Muzny, C. L. Kovar, L. V. Nazareth, R. A. Gibbs, M. J. Ferraro, J. M. Steckelberg, et al. (2009)
J. Bacteriol.
191, 6643-6653
|Abstract »|Full Text »|PDF »
Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein.
M. Kankainen, L. Paulin, S. Tynkkynen, I. von Ossowski, J. Reunanen, P. Partanen, R. Satokari, S. Vesterlund, A. P. A. Hendrickx, S. Lebeer, et al. (2009)
PNAS
106, 17193-17198
|Abstract »|Full Text »|PDF »
The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds.
H. J. Kang, N. G. Paterson, A. H. Gaspar, H. Ton-That, and E. N. Baker (2009)
PNAS
106, 16967-16971
|Abstract »|Full Text »|PDF »
Calcium Is Essential for the Major Pseudopilin in the Type 2 Secretion System.
K. V. Korotkov, M. D. Gray, A. Kreger, S. Turley, M. Sandkvist, and W. G. J. Hol (2009)
J. Biol. Chem.
284, 25466-25470
|Abstract »|Full Text »|PDF »
Acyl Enzyme Intermediates in Sortase-Catalyzed Pilus Morphogenesis in Gram-Positive Bacteria.
I. K. Guttilla, A. H. Gaspar, A. Swierczynski, A. Swaminathan, P. Dwivedi, A. Das, and H. Ton-That (2009)
J. Bacteriol.
191, 5603-5612
|Abstract »|Full Text »|PDF »
Streptococcus Adherence and Colonization.
A. H. Nobbs, R. J. Lamont, and H. F. Jenkinson (2009)
Microbiol. Mol. Biol. Rev.
73, 407-450
|Abstract »|Full Text »|PDF »
Intramolecular Isopeptide Bonds Give Thermodynamic and Proteolytic Stability to the Major Pilin Protein of Streptococcus pyogenes.
Surfome Analysis as a Fast Track to Vaccine Discovery: IDENTIFICATION OF A NOVEL PROTECTIVE ANTIGEN FOR GROUP B STREPTOCOCCUS HYPERVIRULENT STRAIN COH1.
F. Doro, S. Liberatori, M. J. Rodriguez-Ortega, C. D. Rinaudo, R. Rosini, M. Mora, M. Scarselli, E. Altindis, R. D'Aurizio, M. Stella, et al. (2009)
Mol. Cell. Proteomics
8, 1728-1737
|Abstract »|Full Text »|PDF »
Sortase D Forms the Covalent Bond That Links BcpB to the Tip of Bacillus cereus Pili.
J. M. Budzik, S.-Y. Oh, and O. Schneewind (2009)
J. Biol. Chem.
284, 12989-12997
|Abstract »|Full Text »|PDF »
LOCP--locating pilus operons in Gram-positive bacteria.
I. Plyusnin, L. Holm, and M. Kankainen (2009)
Bioinformatics
25, 1187-1188
|Abstract »|Full Text »|PDF »
Mutational Analysis of a Conserved Glutamic Acid Required for Self-Catalyzed Cross-Linking of Bacteriophage HK97 Capsids.
L. E. Dierkes, C. L. Peebles, B. A. Firek, R. W. Hendrix, and R. L. Duda (2009)
J. Virol.
83, 2088-2098
|Abstract »|Full Text »|PDF »
Crystal Structure of FadA Adhesin from Fusobacterium nucleatum Reveals a Novel Oligomerization Motif, the Leucine Chain.
S. Nithianantham, M. Xu, M. Yamada, A. Ikegami, M. Shoham, and Y. W. Han (2009)
J. Biol. Chem.
284, 3865-3872
|Abstract »|Full Text »|PDF »
Mode of Expression and Functional Characterization of FCT-3 Pilus Region-Encoded Proteins in Streptococcus pyogenes Serotype M49.
M. Nakata, T. Koller, K. Moritz, D. Ribardo, L. Jonas, K. S. McIver, T. Sumitomo, Y. Terao, S. Kawabata, A. Podbielski, et al. (2009)
Infect. Immun.
77, 32-44
|Abstract »|Full Text »|PDF »
Identification and phenotypic characterization of a second collagen adhesin, Scm, and genome-based identification and analysis of 13 other predicted MSCRAMMs, including four distinct pilus loci, in Enterococcus faecium.
J. Sillanpaa, S. R. Nallapareddy, V. P. Prakash, X. Qin, M. Hook, G. M. Weinstock, and B. E. Murray (2008)
Microbiology
154, 3199-3211
|Abstract »|Full Text »|PDF »
From the Cover: The molecular switch that activates the cell wall anchoring step of pilus assembly in gram-positive bacteria.