The GA module, a mobile albumin‐binding bacterial domain, adopts a three‐helix‐bundle structure

Johansson, Maria U.; Château, Maarten de; Björck, Lars; Forsén, Sture; Drakenberg, Torbjörn; Wikström, Mats

doi:10.1016/0014-5793(95)01121-t

Cited by 24 publications

(40 citation statements)

References 53 publications

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“…This and the physical properties of the proline residue (29) should contribute to the absence of structure in this peptide. Structural studies on the Ig light chain-binding B domains of protein L (19) and the albuminbinding GA module of protein PAB (20), have revealed that the folded parts are flanked by flexible regions. The Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of interdomain sequences promoting the intronless evolution of a bacterial protein family.

Château

Björck

1996

Proc. Natl. Acad. Sci. U.S.A.

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In the evolution of eukaryotic genes, introns are believed to have played a major role in increasing the probability of favorable duplication events, chance recoinbinations, and exon shuffling resulting in functional hybrid proteins. As a rule, prokaryotic genes lack introns, and the examples of prokaryotic introns described do not seem to have contributed to gene evolution by exon shuffling. Still, certain protein families in modern bacteria evolve rapidly by recombination of genes, duplication offunctional domains, and as shown for protein PAB of the anaerobic bacterial species Pepostrptococcus magnws, by the shuffling of an albumin-binding protein module from group C and G streptococci. Characterization of a protein PAB-related gene in a P. magnus strain with less albumnbinding activity revealed that the shuffled module was missing. Based on this fact and observations made when comparing gene sequences of this family of bacterial surface proteins interacting with albumin and/or immunoglobulin, a model is presented that can explain how this rapid intronless evolution takes place. A new kind of genetic element is introduced: the recer sequence promoting interdomain, in frame recombination and acting as a structureless flexibility-promoting spacer in the corresponding protein.The data presented also suggest that antibiotics could represent the selective pressure behind the shuffling of protein modules in P. magnus, a member of the indigenous bacterial flora.Up-to-date numerous Gram-positive bacterial surface proteins have been described that share common functional traits and structural motifs (1). They are elongated, fibrous proteins anchored in the lipid bilayer of the cell membrane and the peptidoglycan of the cell wall by well-conserved regions. These regions, together with the equally conserved signal peptide, constitute the framework regions of these proteins. The part of the proteins that extend beyond the cell wall into the environment of the bacterium is built up of a distal variable NH2-terminal region followed by domains showing high and specific affinity for abundant host proteins such as human serum albumin (HSA) and IgG. Thus, these proteins assert at least part of their function by binding host proteins to the surface of the bacterium. The functional consequences of these interactions remain unclear, but the coating of a microorganism with host proteins should influence the host-parasite relationship. The gene structure of one of these proteins, the albuminbinding protein PAB of Peptostreptococcus magnus, has been shown to contain a functional domain of 45 amino acid residues responsible for the binding of HSA. This domain is closely related to the HSA-binding domains of protein G, an IgG-and HSA-binding protein of group C and G streptococci (2-4). It was called the GA (protein G-related albuminbinding) module as it was shown to be mobile, i.e., shuffled between genes of different bacterial species, thereby representing the first contemporary example of module shuffling (5). Domains are re...

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Section: Resultsmentioning

confidence: 99%

Identification of interdomain sequences promoting the intronless evolution of a bacterial protein family.

Château

Björck

1996

Proc. Natl. Acad. Sci. U.S.A.

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“…The numbers above the ALB8-GA sequence are used in the text to refer to individual residues of each construct. The numbering corresponds to a subtraction of six from every residue number in our previous papers regarding ALB8-GA (13,26). The ALB8-GA construct contains residues 213-265 of intact protein PAB (11).…”

Section: Resultsmentioning

confidence: 99%

“…G148-GA3 Exhibits High Thermal Stability-CD measurements were performed to investigate the thermal stability of G148-GA3 and to enable comparison with the remarkable thermal stability of ALB8-GA (26). Both G148-GA3 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…15 and present study), like ALB8-GA (13,26), has a similar threehelix bundle structure as the IgG binding domains (34) of protein A from S. aureus (designated E, D, A, B, and C from the N terminus), even though they display different binding properties and show no sequence homology. These three three-helix bundles all show high temperature stability (Refs.…”

Section: N-mentioning

confidence: 99%

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Structure, Specificity, and Mode of Interaction for Bacterial Albumin-binding Modules

Johansson¹,

Frick²,

Nilsson³

et al. 2002

Journal of Biological Chemistry

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We have determined the solution structure of an albumin binding domain of protein G, a surface protein of group C and G streptococci. We find that it folds into a left handed three-helix bundle similar to the albumin binding domain of protein PAB from Peptostreptococcus magnus. The two domains share 59% sequence identity, are thermally very stable, and bind to the same site on human serum albumin. The albumin binding site, the first determined for this structural motif known as the GA module, comprises residues spanning the first loop to the beginning of the third helix and includes the most conserved region of GA modules. The two GA modules have different affinities for albumin from different species, and their albumin binding patterns correspond directly to the host specificity of C/G streptococci and P. magnus, respectively. These studies of the evolution, structure, and binding properties of the GA module emphasize the power of bacterial adaptation and underline ecological and medical problems connected with the use of antibiotics.In the complex molecular interplay between a pathogen and its human host, protein-protein interactions play important roles. For instance, bacteria express surface proteins that interact with abundant human extracellular proteins with high affinity and specificity. In human plasma, albumin (HSA) 1 and immunoglobulins (Ig) are the quantitatively dominating proteins, and significant human pathogens have developed surface proteins that bind these and other plasma proteins (for references, see Ref 1). Two of the most well known such proteins are protein A of Staphylococcus aureus (2) and protein G of group C and G streptococci (3, 4), which both bind to the Fc region of IgG. In 1980, Myhre and Kronvall (5) reported that HSA could bind to the surface of various streptococcal species, including group C and G streptococci. It was later found that protein G was responsible also for the interaction with HSA (6). Protein G has separate binding domains for IgG and HSA (7,8), and as a result C and G streptococci are in vivo covered with an inner layer of IgG and an outer layer of HSA. Peptostreptococcus magnus are strictly anaerobic bacteria that are part of the indigenous human flora of the skin, oral cavity, and gastrointestinal and urogenital tracts. Some isolates of this species bind HSA (9), and notably these isolates are mostly from patients with deep wound infections (10), suggesting that HSA binding turns the commensal P. magnus into a potential pathogen. The surface protein of P. magnus binding HSA is called PAB, and it contains a domain of 45 residues showing a high degree of sequence homology with the HSA binding domains of protein G (11). Analysis of the gene encoding PAB suggested that this domain originates from protein G and has been transferred to and introduced into the pab gene through the action of a conjugational plasmid (related to pCF10 of Enterococcus faecalis) followed by a recombinational event (11). This interspecies exchange of a structurally well defined motif repre...

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“…The albumin-binding protein G of group G streptococcal strain G148 carries three GA modules in the NH 2 -terminal part of the protein showing up to 60% identity to the shuffled module of protein PAB, indicating that protein G might be the source of the GA module in protein PAB. The secondary structure and global fold of the GA module in protein PAB have been determined by NMR and were shown to adopt a 3-helix bundle (22), and the third GA module of protein G was recently shown to exhibit the same structure (23). The predecessor of protein PAB has also been identified.…”

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Protein PAB, an Albumin-binding Bacterial Surface Protein Promoting Growth and Virulence

Château¹,

Holst

Björck³

1996

Journal of Biological Chemistry

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The anaerobic bacterium Peptostreptococcus magnus is a human commensal and pathogen. Previous work has shown that strains of P. magnus isolated from patients with gynecological disease (vaginosis) frequently express an immunoglobulin (Ig) light chain-binding protein called protein L. Here we report that strains isolated from localized suppurative infections bind human serum albumin (HSA), whereas commensal isolates bind neither Ig nor HSA. The HSA-binding protein PAB was extracted from the bacterial surface or isolated from the culture supernatant of the P. magnus strain ALB8. Protein PAB was shown to have two homologous HSA-binding domains, GA and uGA. GA is absent in the sequence of a related protein from another P. magnus strain and shows a high degree of homology to the HSA-binding domains of streptococcal protein G. Therefore GA is believed to have recently been shuffled as a module from genes of other bacterial species into the protein PAB gene. This GA module was shown to exhibit a much higher affinity for HSA than uGA and was also found to be present in all of the isolates tested from localized suppurative infections, indicating a role in virulence. Moreover, when peptostreptococci or streptococci expressing the GA module were grown in the presence of HSA, the growth rate was substantially increased. Thus, the HSA binding activity of the GA module adds selective advantages to the bacteria, which increases their virulence in the case of P. magnus strains.

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The GA module, a mobile albumin‐binding bacterial domain, adopts a three‐helix‐bundle structure

Cited by 24 publications

References 53 publications

Identification of interdomain sequences promoting the intronless evolution of a bacterial protein family.

Identification of interdomain sequences promoting the intronless evolution of a bacterial protein family.

Structure, Specificity, and Mode of Interaction for Bacterial Albumin-binding Modules

Protein PAB, an Albumin-binding Bacterial Surface Protein Promoting Growth and Virulence

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