ArticleProceedings of the National Academy of Sciences of the United States of America2014
Autocatalytically generated Thr-Gln ester bond cross-links stabilize the repetitive Ig-domain shaft of a bacterial cell surface adhesin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
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- Rational Design and One-Step Immobilization of Chitosanase for Specific and Recyclable Chitobiose Production.Foods (Basel, Switzerland) · 2025Article
- A global survey of intramolecular isopeptide bonds.Protein science : a publication of the Protein Society · 2025Article
- Protease mimicry: Dissecting the ester bond crosslinking mechanics in bacterial adhesin proteins.Protein science : a publication of the Protein Society · 2025Article
- Domain structure and cross-linking in a giant adhesin from the Mobiluncus mulieris bacterium.Acta crystallographica. Section D, Structural biology · 2023Article
- Ester Bonds for Modulation of the Mechanical Properties of Protein Hydrogels.International journal of molecular sciences · 2023Article
- Orthogonal Crosslinking: A Strategy to Generate Novel Protein Topology and Function.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Peptide/protein-based macrocycles: from biological synthesis to biomedical applications.RSC chemical biology · 2022Review
- An ester bond underlies the mechanical strength of a pathogen surface protein.Nature communications · 2021Article
- Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens.Diagnostics (Basel, Switzerland) · 2021Review
- Structure and chemistry of lysinoalanine crosslinking in the spirochaete flagella hook.Nature chemical biology · 2019Article
- A new structural class of bacterial thioester domains reveals a slipknot topology.Protein science : a publication of the Protein Society · 2018Article
- Conditionally disordered proteins: bringing the environment back into the fold.Cellular and molecular life sciences : CMLS · 2017Review
- Pilus biogenesis of Gram-positive bacteria: Roles of sortases and implications for assembly.Protein science : a publication of the Protein Society · 2017Review
- Autocatalytic association of proteins by covalent bond formation: a Bio Molecular Welding toolbox derived from a bacterial adhesin.Scientific reports · 2017Article
- Engineering a Lys-Asn isopeptide bond into an immunoglobulin-like protein domain enhances its stability.Scientific reports · 2017Article
- Article
- Convergent weaponry in a biological arms race.eLife · 2015Article
- Article
- Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein.Nature communications · 2015Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gram-positive bacteria are decorated by a variety of proteins that are anchored to the cell wall and project from it to mediate colonization, attachment to host cells, and pathogenesis. These proteins, and protein assemblies, such as pili, are typically long and thin yet must withstand high levels of mechanical stress and proteolytic attack. The recent discovery of intramolecular isopeptide bond cross-links, formed autocatalytically, in the pili from Streptococcus pyogenes has highlighted the role that such cross-links can play in stabilizing such structures. We have investigated a putative cell-surface adhesin from Clostridium perfringens comprising an N-terminal adhesin domain followed by 11 repeat domains. The crystal structure of a two-domain fragment shows that each domain has an IgG-like fold and contains an unprecedented ester bond joining Thr and Gln side chains. MS confirms the presence of these bonds. We show that the bonds form through an autocatalytic intramolecular reaction catalyzed by an adjacent His residue in a serine protease-like mechanism. Two buried acidic residues assist in the reaction. By mutagenesis, we show that loss of the ester bond reduces the thermal stability drastically and increases susceptibility to proteolysis. As in pilin domains, the bonds are placed at a strategic position joining the first and last strands, even though the Ig fold type differs. Bioinformatic analysis suggests that similar domains and ester bond cross-links are widespread in Gram-positive bacterial adhesins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.