The solution structure of the active domain of CAP18 — a lipopolysaccharide binding protein from rabbit leukocytes

Chen, Chinpan; Brock, Roland; Luh, Frederick Y.; Chou, Ping Jung; Larrick, James W.; Huang, Rong; Huang, Tai Huang

doi:10.1016/0014-5793(95)00792-8

Cited by 63 publications

(58 citation statements)

References 20 publications

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“…The formation of an amphipathic, ␣-helical structure and its relationship to the bactericidal activity of the cathelicidins has been the subject of previous studies (1,8,12,17,36). In this study, we analyzed five synthetic peptides (CAP18, CAP18 21a , CAP18 18 , CAP18 15a , and CAP18 17 ) by CD spectroscopy.…”

Section: Resultsmentioning

confidence: 99%

“…Homologs of CAP18 have since been identified in other species including humans (FALL39/LL37) (1, 19), mice (mCRAMP) (12, 30), rats (rCRAMP), and sheep (SMAP29 and SMAP34) (2,16,25,34). Circular dichroism (CD) measurements indicate that these linear peptides adopt ␣-helical structure in some solvents (1,8,12,17,36). These cathelicidinderived peptides kill bacteria by disrupting the bacterial membrane (28).…”

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confidence: 99%

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Bactericidal Activity of Mammalian Cathelicidin-Derived Peptides

Travis¹,

Anderson²,

Forsyth³

et al. 2000

Infect Immun

342

299

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Endogenous antimicrobial peptides of the cathelicidin family contribute to innate immunity. The emergence of widespread antibiotic resistance in many commonly encountered bacteria requires the search for new bactericidal agents with therapeutic potential. Solid-phase synthesis was employed to prepare linear antimicrobial peptides found in cathelicidins of five mammals: human (FALL39/LL37), rabbit (CAP18), mouse (mCRAMP), rat (rCRAMP), and sheep (SMAP29 and SMAP34). These peptides were tested at ionic strengths of 25 and 175 mM against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Each peptide manifested activity against P. aeruginosa irrespective of the NaCl concentration. CAP18 and SMAP29 were the most effective peptides of the group against all test organisms under both lowand high-salt conditions. Select peptides of 15 to 21 residues, modeled on CAP18 (37 residues), retained activity against the gram-negative bacteria and methicillin-sensitive S. aureus, although the bactericidal activity was reduced compared to that of the parent peptide. In accordance with the behavior of the parent molecule, the truncated peptides adopted an ␣-helical structure in the presence of trifluoroethanol or lipopolysaccharide. The relationship between the bactericidal activity and several physiochemical properties of the cathelicidins was examined. The activities of the full-length peptides correlated positively with a predicted gradient of hydrophobicity along the peptide backbone and with net positive charge; they correlated inversely with relative abundance of anionic residues. The salt-resistant, antimicrobial properties of CAP18 and SMAP29 suggest that these peptides or congeneric structures have potential for the treatment of bacterial infections in normal and immunocompromised persons and individuals with cystic fibrosis.The rapidly expanding prevalence of bacterial strains resistant to conventional antibiotics has prompted a search for new therapeutic agents, including various antimicrobial peptides of animal origin (15). Two broad classes of mammalian antibacterial peptides have been especially well studied: the cysteinerich ␣-and ␤-defensins and various cathelicidins (6,13,22,26,27,41,42). Both classes are produced as precursors that require proteolytic processing to generate the mature antimicrobial peptide. Cathelicidins contain an N-terminal domain called cathelin, for which no function has yet been ascribed, and a C-terminal domain that comprises an antimicrobial peptide (reviewed in references 41 and 42). While the cathelin domains are highly conserved across species, the C-terminal antimicrobial domains are structurally diverse. The first cathelicidin precursor to be described was rabbit CAP18 (20), and its mature peptide was shown to have broad-spectrum bactericidal activity (19). Homologs of CAP18 have since been identified in other species including humans (FALL39/LL37) (1, 19), mice (mCRAMP) (12, 30), rats (rCRAMP), and sheep (SMAP29 and SMAP34...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Bactericidal Activity of Mammalian Cathelicidin-Derived Peptides

Travis¹,

Anderson²,

Forsyth³

et al. 2000

Infect Immun

342

299

View full text Add to dashboard Cite

show abstract

“…37 It consisted of mutant GFPs called Cerulean 38 and Venus 39 linked by a stable alpha-helix. 40 We picked this linker because the helix with a length (5 nm) equal to the characteristic distance (R o ) for energy transfer for those fluorophores and it is stable. Equation 1 shows that when R, the distance between donor and acceptor, is equal to R o there is 50% energy transfer: We created a transgenic mouse line with actinin-sstFRET by randomly incorporating the construct into genome using the pronucleus method.…”

Section: Transforming Mechanical Forces Into Optical Signalsmentioning

confidence: 99%

Genetically encoded force sensors for measuring mechanical forces in proteins

Wang

Meng

Sachs

2011

Communicative & Integrative Biology

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“…Short antimicrobial peptides in an amphipathic environment predominantly fold into ␣-helical (e.g. magainin, CAP18 106 -137 (35)), ␤-hairpin (e.g. protegrin, tachyplesin (36)), or extended (V-type) conformation (e.g.…”

Section: Interaction Of Peptide With Anionic and Zwitterionic Micellementioning

confidence: 99%

Structural Origin of Endotoxin Neutralization and Antimicrobial Activity of a Lactoferrin-based Peptide

Japelj

Pristovšek

Majerle

et al. 2005

Journal of Biological Chemistry

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Treatment of Gram-negative bacterial infections with antimicrobial agents can cause release of the endotoxin lipopolysaccharide (LPS), the potent initiator of sepsis, which is the major cause of mortality in intensive care units worldwide. Structural information on peptides bound to LPS can lead to the development of more effective endotoxin neutralizers. Short linear antimicrobial and endotoxin-neutralizing peptide LF11, based on the human lactoferrin, binds to LPS, inducing a peptide fold with a "T-shaped" arrangement of a hydrophobic core and two clusters of basic residues that match the distance between the two phosphate groups of LPS. Side chain arrangement of LF11 bound to LPS extends the previously proposed LPS binding pattern, emphasizing the importance of both electrostatic and hydrophobic interactions in a defined geometric arrangement. In anionic micelles, the LF11 forms amphipathic conformation with a smaller hydrophobic core than in LPS, whereas in zwitterionic micelles, the structure is even less defined. Protection of tryptophan fluorescence quenching in the order SDS>LPS>DPC and hydrogen exchange protection indicates the decreasing extent of insertion of the N terminus and potential role of peptide plasticity in differentiation between bacterial and eukaryotic membranes. Bacterial lipopolysaccharide (LPS)1 is one of the most potent inducers of the innate immune response. In contrast to the adaptive immune system, innate immunity engaging "pattern recognition receptors" recognizes the conserved motif of molecules characteristic for the pathogens. Pathogen-associated molecular patterns, rather than highly variable strain-specific molecules, allow recognition and response to the broad range of pathogens. Recognition of various forms of LPS from different strains of Gram-negative bacteria, where the lipid A moiety represents the pathogen-associated molecular pattern, triggers the signaling cascade, resulting in release of pro-inflammatory mediators, such as cytokines, as well as small molecules, such as lipid mediators and reactive oxygen species (1). In advanced stages of sepsis, when the immune response is overstimulated and deregulated, the pathological consequences are so diverse (ranging from hypotension to intravascular coagulation and multiple organ failure) that treatment of a single target, such as tumor necrosis factor ␣, is insufficient. Sepsis claims each year more than 200,000 lives in the United States alone. Mortality of patients with sepsis is still above 30% and higher in the elderly (2), in large extent due to the lack of the effective treatment of the underlying pathology. The preferable treatment, at early stages of sepsis, or prevention, in the case of high risk of sepsis, might be to combine antimicrobial activity to destroy bacteria with neutralization of endotoxin to prevent its interaction with serum and cellular receptors (such as LBP, CD14, and the MD2/TLR4 complex (3)), which directly recognize endotoxin and initiate the immune response. The small cyclic lipopeptide polymy...

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The solution structure of the active domain of CAP18 — a lipopolysaccharide binding protein from rabbit leukocytes

Cited by 63 publications

References 20 publications

Bactericidal Activity of Mammalian Cathelicidin-Derived Peptides

Bactericidal Activity of Mammalian Cathelicidin-Derived Peptides

Genetically encoded force sensors for measuring mechanical forces in proteins

Structural Origin of Endotoxin Neutralization and Antimicrobial Activity of a Lactoferrin-based Peptide

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