ArticleAmino acids2012
The α-defensin salt-bridge induces backbone stability to facilitate folding and confer proteolytic resistance.
Article in Amino acids, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Exploring the Terra incognita of AI-based domain classifications.Protein science : a publication of the Protein Society · 2025Article
- Antimicrobial peptides: structure, functions and translational applications.Nature reviews. Microbiology · 2025Review
- Deciphering the folding code of collagens.Nature communications · 2025Article
- Antimicrobial Peptide Synergies for Fighting Infectious Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- The C-Terminus of Panusin, a Lobster β-Defensin, Is Crucial for Optimal Antimicrobial Activity and Serum Stability.Pharmaceutics · 2023Article
- Mouse α-Defensins: Structural and Functional Analysis of the 17 Cryptdin Isoforms Identified from a Single Jejunal Crypt.Infection and immunity · 2023Article
- The function of peptide-mimetic anionic groups and salt bridges in the antimicrobial activity and conformation of cationic amphiphilic copolymers.RSC advances · 2021Article
- Targeting and inactivation of bacterial toxins by human defensins.Biological chemistry · 2017Review
- Human Neuronal Calcium Sensor-1 Protein Avoids Histidine Residues To Decrease pH Sensitivity.The journal of physical chemistry. B · 2017Article
- Influence of Glu/Arg, Asp/Arg, and Glu/Lys Salt Bridges on α-Helical Stability and Folding Kinetics.Biophysical journal · 2016Article
- Salt bridge as a gatekeeper against partial unfolding.Protein science : a publication of the Protein Society · 2016Article
- Temperature-Dependent Conformational Properties of Human Neuronal Calcium Sensor-1 Protein Revealed by All-Atom Simulations.The journal of physical chemistry. B · 2016Article
- The Unusual Resistance of Avian Defensin AvBD7 to Proteolytic Enzymes Preserves Its Antibacterial Activity.PloS one · 2016Article
- Free energy landscape of a minimalist salt bridge model.Protein science : a publication of the Protein Society · 2016Article
- Effects of the C-Terminal Tail on the Conformational Dynamics of Human Neuronal Calcium Sensor-1 Protein.The journal of physical chemistry. B · 2015Article
- Hydrophobic determinants of α-defensin bactericidal activity.Infection and immunity · 2014Article
- Solvent-Exposed Salt Bridges Influence the Kinetics of α-Helix Folding and Unfolding.The journal of physical chemistry letters · 2014Article
- Rattusin, an intestinal α-defensin-related peptide in rats with a unique cysteine spacing pattern and salt-insensitive antibacterial activities.Antimicrobial agents and chemotherapy · 2013Article
- Conopeptide ρ-TIA defines a new allosteric site on the extracellular surface of the α1B-adrenoceptor.The Journal of biological chemistry · 2013Article
- NMR solution structure and condition-dependent oligomerization of the antimicrobial peptide human defensin 5.Biochemistry · 2012Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Salt-bridge interactions between acidic and basic amino acids contribute to the structural stability of proteins and to protein-protein interactions. A conserved salt-bridge is a canonical feature of the α-defensin antimicrobial peptide family, but the role of this common structural element has not been fully elucidated. We have investigated mouse Paneth cell α-defensincryptdin-4 (Crp4) and peptide variants with mutations at Arg7 or Glu15 residue positions to disrupt the salt-bridge and assess the consequences on Crp4 structure, function, and stability. NMR analyses showed that both (R7G)-Crp4 and (E15G)-Crp4 adopt native-like structures, evidence of fold plasticity that allows peptides to reshuffle side chains and stabilize the structure in the absence of the salt-bridge. In contrast, introduction of a large hydrophobic side chain at position 15, as in (E15L)-Crp4 cannot be accommodated in the context of the Crp4 primary structure. Regardless of which side of the salt-bridge was mutated, salt-bridge variants retained bactericidal peptide activity with differential microbicidal effects against certain bacterial cell targets, confirming that the salt-bridge does not determine bactericidal activity per se. The increased structural flexibility induced by salt-bridge disruption enhanced peptide sensitivity to proteolysis. Although sensitivity to proteolysis by MMP7 was unaffected by most Arg(7) and Glu(150 substitutions, every salt-bridge variant was degraded extensively by trypsin. Moreover, the salt-bridge facilitates adoption of the characteristic α-defensin fold as shown by the impaired in vitro refolding of (E15D)-proCrp4, the most conservative salt-bridge disrupting replacement. In Crp4, therefore, the canonical α-defensin salt-bridge facilitates adoption of the characteristic α-defensin fold, which decreases structural flexibility and confers resistance todegradation by proteinases.
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