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Structural and functional studies of streptococcal surface adhesins
Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The oral cavity is home to an array of microorganisms that are associated with dental plaque. Some Gram-positive bacteria are common inhabitants of the oral cavity and in order to colonize such a unique environment adhesion becomes essential and is accomplish by adhesins expressed on the bacterial surface. Adhesins can interact with host molecules or with structures on the resident oral microbial flora. Members of the antigen I/II (AgI/II) protein family are commonly found on the surface of oral streptococci and have the unique feature that their putative adhesin domain is located in the centre of the primary sequence. Crystal structures representing parts of the C-terminal domains from two AgI/II members, SpaP from Streptococcus mutans and AspA from Streptococcus pyogenes, were determined to 2.2 and 1.8 Å resolution respectively. The structures are very similar and consist of two domains with DEv-IgG folds. The proteins are stabilized by intramolecular isopeptide bonds and tightly coordinated metal ions.

Another group of surface proteins is the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) that have their putative adhesin domain in the N-terminal, presented on a stalk formed by multiples of repeated C-terminal domains. Sgo0707 from Streptococcus gordonii is an example of this group of proteins and its N-terminal domain was determined to 2.1 Å resolution. The structure consists of two domains, N1 and N2, both of which adopt β-sandwiches. In the Sgo0707 structure no isopeptide bonds or metal ions were detected. A putative binding cleft is present in the N1 domain. Functional studies revealed collagen type-1 and keratinocytes as possible binding partners.

In order to further characterize the AgI/II protein AspA from S. pyogenes a long form of the protein, AspA-AVPC, was expressed and purified. During the purification process it was observed that the protein fragmented into two major parts. This process could be inhibited by the addition of 0.5 mM EDTA during protein purification.

In conclusion, these studies have resulted in adding to the knowledge of protein structures and function of streptococcal surface proteins.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2013. , 41 p.
Series
Umeå University odontological dissertations, ISSN 0345-7532 ; 126
National Category
Structural Biology
Identifiers
URN: urn:nbn:se:umu:diva-78920ISBN: 978-7459-689-2 OAI: oai:DiVA.org:umu-78920DiVA: diva2:638210
Public defence
2013-09-12, Sal 9D, Tandläkarhögskolan 9 tr, Norrlands universitetssjukhus, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2013-08-15 Created: 2013-07-25 Last updated: 2013-09-27Bibliographically approved
List of papers
1. Structure of the C-terminal domain of the surface antigen SpaP from the caries pathogen Streptococcus mutans
Open this publication in new window or tab >>Structure of the C-terminal domain of the surface antigen SpaP from the caries pathogen Streptococcus mutans
2011 (English)In: Acta Crystallographica. Section F: Structural Biology and Crystallization Communications, ISSN 1744-3091, E-ISSN 1744-3091, Vol. 67, 23-26 p.Article in journal (Refereed) Published
Abstract [en]

SpaP is a 1500-residue adhesin expressed on the surface of the caries-implicated bacterium Streptococcus mutans. SpaP is a member of the antigen I/II (AgI/II) family of proteins expressed by oral streptococci. These surface proteins are crucial for the incorporation of streptococci into dental plaque. The structure of the C-terminal domain of SpaP (residues 1136-1489) was solved and refined to 2.2 Å resolution with six molecules in the asymmetric unit. Similar to a related AgI/II structure, SpaP is stabilized by isopeptide bonds between lysine and asparagine side chains.

Place, publisher, year, edition, pages
International Union of Crystallography, 2011
Keyword
adhesin, caries, protein crystallography
National Category
Biochemistry and Molecular Biology Dentistry
Research subject
Molecular Biology; Infectious Diseases; Odontology
Identifiers
urn:nbn:se:umu:diva-40180 (URN)10.1107/S174430911004443X (DOI)
Funder
Swedish Research Council
Available from: 2011-02-18 Created: 2011-02-16 Last updated: 2017-12-11Bibliographically approved
2. Structural and functional analysis of the N-terminal domain of the Streptococcus gordonii adhesin Sgo0707
Open this publication in new window or tab >>Structural and functional analysis of the N-terminal domain of the Streptococcus gordonii adhesin Sgo0707
Show others...
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 5, e63768- p.Article in journal (Refereed) Published
Abstract [en]

The commensal Streptococcus gordonii expresses numerous surface adhesins with which it interacts with other microorganisms, host cells and salivary proteins to initiate dental plaque formation. However, this Gram-positive bacterium can also spread to non-oral sites such as the heart valves and cause infective endocarditis. One of its surface adhesins, Sgo0707, is a large protein composed of a non-repetitive N-terminal region followed by several C-terminal repeat domains and a cell wall sorting motif. Here we present the crystal structure of the Sgo0707 N-terminal domains, refined to 2.1 Å resolution. The model consists of two domains, N1 and N2. The largest domain, N1, comprises a putative binding cleft with a single cysteine located in its centre and exhibits an unexpected structural similarity to the variable domains of the streptococcal Antigen I/II adhesins. The N2-domain has an IgG-like fold commonly found among Gram-positive surface adhesins. Binding studies performed on S. gordonii wild-type and a Sgo0707 deficient mutant show that the Sgo0707 adhesin is involved in binding to type-1 collagen and to oral keratinocytes.

Place, publisher, year, edition, pages
Public Library Science, 2013
Keyword
crystal structure, adhesin, collagen
National Category
Structural Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:umu:diva-71563 (URN)10.1371/journal.pone.0063768 (DOI)000319107900058 ()
Funder
Swedish Research Council, 2011-4186
Available from: 2013-06-03 Created: 2013-06-03 Last updated: 2017-12-06Bibliographically approved
3. Expression and purification of Streptococcus pyogenes adhesin AspA
Open this publication in new window or tab >>Expression and purification of Streptococcus pyogenes adhesin AspA
(English)Manuscript (preprint) (Other academic)
National Category
Structural Biology
Identifiers
urn:nbn:se:umu:diva-79208 (URN)
Available from: 2013-08-13 Created: 2013-08-13 Last updated: 2013-08-13Bibliographically approved
4. Structure of the C-terminal domain of AspA (antigen I/II-family) protein from Streptococcus pyogenes
Open this publication in new window or tab >>Structure of the C-terminal domain of AspA (antigen I/II-family) protein from Streptococcus pyogenes
2014 (English)In: FEBS open Bio, ISSN 2211-5463, Vol. 4, 283-289 p.Article in journal (Refereed) Published
Abstract [en]

The pathogenic bacteria Streptococcus pyogenes can cause an array of diseases in humans, including moderate infections such as pharyngitis (strep throat) as well as life threatening conditions such as necrotizing fasciitis and puerperal fever. The antigen I/II family proteins are cell wall anchored adhesin proteins found on the surfaces of most oral streptococci and are involved in host colonization and biofilm formation. In the present study we have determined the crystal structure of the C2–3-domain of the antigen I/II type protein AspA from S. pyogenes M type 28. The structure was solved to 1.8 Å resolution and shows that the C2–3-domain is comprised of two structurally similar DEv-IgG motifs, designated C2 and C3, both containing a stabilizing covalent isopeptide bond. Furthermore a metal binding site is identified, containing a bound calcium ion. Despite relatively low sequence identity, interestingly, the overall structure shares high similarity to the C2–3-domains of antigen I/II proteins from Streptococcus gordonii and Streptococcus mutans, although certain parts of the structure exhibit distinct features. In summary this work constitutes the first step in the full structure determination of the AspA protein from S. pyogenes.

Place, publisher, year, edition, pages
Elsevier, 2014
Keyword
crystal structure, adhesin, streptococci, isopeptide
National Category
Structural Biology
Research subject
biological chemistry; Biochemistry
Identifiers
urn:nbn:se:umu:diva-79210 (URN)10.1016/j.fob.2014.02.012 (DOI)
Funder
Swedish Research Council, 2011-4186
Available from: 2013-08-13 Created: 2013-08-13 Last updated: 2014-06-16Bibliographically approved

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