M3i

@article{whisstock_serpins_2010,

title = {Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions},

author = {James C Whisstock and Gary A Silverman and Phillip I Bird and Stephen P Bottomley and Dion Kaiserman and Cliff J Luke and Stephen C Pak and Jean-Marc Reichhart and James A Huntington},

doi = {10.1074/jbc.R110.141408},

issn = {1083-351X},

year  = {2010},

date = {2010-08-01},

journal = {J. Biol. Chem.},

volume = {285},

number = {32},

pages = {24307--24312},

abstract = {Inhibitory serpins are metastable proteins that undergo a substantial conformational rearrangement to covalently trap target peptidases. The serpin reactive center loop contributes a majority of the interactions that serpins make during the initial binding to target peptidases. However, structural studies on serpin-peptidase complexes reveal a broader set of contacts on the scaffold of inhibitory serpins that have substantial influence on guiding peptidase recognition. Structural and biophysical studies also reveal how aberrant serpin folding can lead to the formation of domain-swapped serpin multimers rather than the monomeric metastable state. Serpin domain swapping may therefore underlie the polymerization events characteristic of the serpinopathies. Finally, recent structural studies reveal how the serpin fold has been adapted for non-inhibitory functions such as hormone binding.},

keywords = {Animals, Biological, Biological Transport, Biophysics, Catalytic Domain, Hormones, Humans, Kinetics, M3i, Models, Peptide Hydrolases, Protein Binding, Protein Conformation, Protein Structure, reichhart, Serpins, Substrate Specificity, Tertiary, Thrombin},

pubstate = {published},

tppubtype = {article}

}

@article{geotti-bianchini_conformationally_2009,

title = {Conformationally controlled, thymine-based alpha-nucleopeptides},

author = {Piero Geotti-Bianchini and Marco Crisma and Cristina Peggion and Alberto Bianco and Fernando Formaggio},

doi = {10.1039/b822789f},

issn = {1359-7345},

year  = {2009},

date = {2009-01-01},

journal = {Chemical Communications (Cambridge, England)},

number = {22},

pages = {3178--3180},

abstract = {Rigid peptide backbones and backbone-to-side chain H-bonds permit the design of alpha-nucleopeptides with known 3D-structure; thymine-thymine base pairing is also observed.},

keywords = {I2CT, Magnetic Resonance Spectroscopy, Oligopeptides, Protein Conformation, Team-Bianco, thymine, X-Ray Diffraction},

pubstate = {published},

tppubtype = {article}

}

@article{geotti-bianchini_synthesis_2009,

title = {Synthesis and 3D-structure of conformationally controlled nucleo-peptides},

author = {Piero Geotti-Bianchini and Marco Crisma and Cristina Peggion and Alberto Bianco and Fernando Formaggio},

doi = {10.1007/978-0-387-73657-0_16},

issn = {0065-2598},

year  = {2009},

date = {2009-01-01},

journal = {Advances in Experimental Medicine and Biology},

volume = {611},

pages = {37--38},

keywords = {I2CT, Models, Molecular, Nucleoproteins, Peptides, Protein Conformation, Team-Bianco},

pubstate = {published},

tppubtype = {article}

}

@article{pelte_immune_2006,

title = {Immune challenge induces N-terminal cleavage of the Drosophila serpin Necrotic},

author = {Nadège Pelte and Andrew S Robertson and Zhen Zou and Didier Belorgey and Timothy R Dafforn and Haobo Jiang and David Lomas and Jean-Marc Reichhart and David Gubb},

doi = {10.1016/j.ibmb.2005.10.004},

issn = {0965-1748},

year  = {2006},

date = {2006-01-01},

journal = {Insect Biochem. Mol. Biol.},

volume = {36},

number = {1},

pages = {37--46},

abstract = {The Drosophila Necrotic protein is a serine proteinase inhibitor, which regulates the Toll-mediated innate immune response. Necrotic specifically inhibits an extracellular serine proteinase cascade leading to activation of the Toll ligand, Spätzle. Necrotic carries a polyglutamine extension amino-terminal to the core serpin structure. We show here that cleavage of this N-terminal extension occurs following immune challenge. This modification is blocked in PGRP-SA(semmelweiss) mutants after Gram-positive bacterial challenge and in persephone mutants after fungal or Gram-positive bacterial challenge, indicating that activation of either of the Toll pathway upstream branches induces N-terminal cleavage of the serpin. The absolute requirement of persephone gene product for this cleavage indicates that Gram-positive bacteria activate a redundant set of proteinases upstream of Toll. Both full-length Necrotic and the core serpin are active inhibitors of a range of serine proteinases: the highest affinity being for cathepsin G and elastases. We found a 13-fold increase in the specificity of the core serpin over that of full-length Necrotic for one of the tested proteinases (porcine pancreatic elastase). This finding indicates that cleavage of the Necrotic amino-terminal extension might modulate Toll activation following the initial immune response.},

keywords = {Animals, Gene Expression Regulation, M3i, Protein Conformation, reichhart, Serpins, Signal Transduction},

pubstate = {published},

tppubtype = {article}

}

@article{reichhart_tip_2005,

title = {Tip of another iceberg: Drosophila serpins},

author = {Jean-Marc Reichhart},

doi = {10.1016/j.tcb.2005.10.001},

issn = {0962-8924},

year  = {2005},

date = {2005-12-01},

journal = {Trends Cell Biol.},

volume = {15},

number = {12},

pages = {659--665},

abstract = {Serpins are serine protease inhibitors with a conserved structure that have been identified in nearly all species and act as suicide substrates by binding covalently to their target proteases. Serpins regulate various physiological processes and defence mechanisms. In humans, several serpin mutations are linked to diseases. The genome of Drosophila melanogaster encodes 29 serpins and even more serine proteases. To date, three serpins have been investigated in detail. Spn27A controls the Toll pathway during early development and is involved in defence reactions in adult flies. SPN42DaA is an inhibitor of furin, a subtilisin-like convertase that is required for pro-protein maturation. Spn43Ac controls the Toll pathway during the immune response. In each case, Drosophila genetics has shed new light on the function of these serine protease inhibitors.},

keywords = {Animals, Immunity, M3i, Protein Conformation, reichhart, Serine Proteinase Inhibitors, Serpins},

pubstate = {published},

tppubtype = {article}

}

@article{fournel_c3-symmetric_2005,

title = {C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L},

author = {Sylvie Fournel and Sébastien Wieckowski and Weimin Sun and Nathalie Trouche and Hélène Dumortier and Alberto Bianco and Olivier Chaloin and Mohammed Habib and Jean-Christophe Peter and Pascal Schneider and Bernard Vray and René E Toes and Rienk Offringa and Cornelis J M Melief and Johan Hoebeke and Gilles Guichard},

doi = {10.1038/nchembio746},

issn = {1552-4450},

year  = {2005},

date = {2005-12-01},

journal = {Nature Chemical Biology},

volume = {1},

number = {7},

pages = {377--382},

abstract = {Interaction between CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, and its ligand CD40L, a 39-kDa glycoprotein, is essential for the development of humoral and cellular immune responses. Selective blockade or activation of this pathway provides the ground for the development of new treatments against immunologically based diseases and malignancies. Like other members of the TNF superfamily, CD40L monomers self-assemble around a threefold symmetry axis to form noncovalent homotrimers that can each bind three receptor molecules. Here, we report on the structure-based design of small synthetic molecules with C3 symmetry that can mimic CD40L homotrimers. These molecules interact with CD40, compete with the binding of CD40L to CD40, and reproduce, to a certain extent, the functional properties of the much larger homotrimeric soluble CD40L. Architectures based on rigid C3-symmetric cores may thus represent a general approach to mimicking homotrimers of the TNF superfamily.},

keywords = {Animals, Apoptosis, Biological, CD40 Antigens, CD40 Ligand, Cell Line, Dumortier, Humans, I2CT, Inbred BALB C, Mice, Models, Molecular Mimicry, Molecular Structure, Peptides, Protein Conformation, Protein Structure, Quaternary, Structure-Activity Relationship, Team-Bianco, Team-Dumortier, Time Factors, tumor},

pubstate = {published},

tppubtype = {article}

}

@article{fournel_c3-symmetric_2005b,

title = {C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L},

author = {Sylvie Fournel and Sébastien Wieckowski and Weimin Sun and Nathalie Trouche and Hélène Dumortier and Alberto Bianco and Olivier Chaloin and Mohammed Habib and Jean-Christophe Peter and Pascal Schneider and Bernard Vray and René E Toes and Rienk Offringa and Cornelis J M Melief and Johan Hoebeke and Gilles Guichard},

doi = {10.1038/nchembio746},

issn = {1552-4450},

year  = {2005},

date = {2005-01-01},

journal = {Nature Chemical Biology},

volume = {1},

number = {7},

pages = {377--382},

abstract = {Interaction between CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, and its ligand CD40L, a 39-kDa glycoprotein, is essential for the development of humoral and cellular immune responses. Selective blockade or activation of this pathway provides the ground for the development of new treatments against immunologically based diseases and malignancies. Like other members of the TNF superfamily, CD40L monomers self-assemble around a threefold symmetry axis to form noncovalent homotrimers that can each bind three receptor molecules. Here, we report on the structure-based design of small synthetic molecules with C3 symmetry that can mimic CD40L homotrimers. These molecules interact with CD40, compete with the binding of CD40L to CD40, and reproduce, to a certain extent, the functional properties of the much larger homotrimeric soluble CD40L. Architectures based on rigid C3-symmetric cores may thus represent a general approach to mimicking homotrimers of the TNF superfamily.},

keywords = {Animals, Apoptosis, Biological, CD40 Antigens, CD40 Ligand, Cell Line, Humans, I2CT, Inbred BALB C, Mice, Models, Molecular Mimicry, Molecular Structure, Peptides, Protein Conformation, Protein Structure, Quaternary, Structure-Activity Relationship, Team-Bianco, Time Factors, tumor},

pubstate = {published},

tppubtype = {article}

}

@article{lancelot_characterization_2003,

title = {Characterization of the 310-helix in model peptides by HRMAS NMR spectroscopy},

author = {Nathalie Lancelot and Karim Elbayed and Jésus Raya and Martial Piotto and Jean-Paul Briand and Fernando Formaggio and Claudio Toniolo and Alberto Bianco},

doi = {10.1002/chem.200390151},

issn = {0947-6539},

year  = {2003},

date = {2003-03-01},

journal = {Chemistry (Weinheim an Der Bergstrasse, Germany)},

volume = {9},

number = {6},

pages = {1317--1323},

abstract = {A tetra- and a hepta-homopeptide from the C(alpha)-tetrasubstituted Aib (alpha-aminoisobutyric acid) residue were covalently linked to the POEPOP resin by the fragment-condensation approach. The conformational preferences of the two model peptides were determined for the first time on a solid support by means of high-resolution magic angle spinning NMR spectroscopy. The results obtained indicate that the Aib homopeptides adopt a regular 3(10)-helical structure even when they are covalently bound to a polymeric matrix, and thus confirm the remarkable conformational stability of the peptides rich in this amino acid. An ATR-FTIR spectroscopic investigation, performed in parallel, also confirmed that these polymer-bound peptides do indeed adopt a helical conformation. The results of this study open the possibility to exploit the peptide-resin conjugates based on C(alpha)-tetrasubstituted alpha-amino acids as helpful, structurally organized templates in molecular recognition studies or as catalysts in asymmetric synthesis.},

keywords = {biomolecular, Fourier Transform Infrared, I2CT, Nuclear Magnetic Resonance, Peptides, Protein Conformation, spectroscopy, Team-Bianco},

pubstate = {published},

tppubtype = {article}

}

@article{lamberty_insect_2001,

title = {Insect immunity. Constitutive expression of a cysteine-rich antifungal and a linear antibacterial peptide in a termite insect.},

author = {M Lamberty and Daniel Zachary and R Lanot and C Bordereau and A Robert and Jules A Hoffmann and Philippe Bulet},

doi = {10.1074/jbc.M002998200},

issn = {0021-9258},

year  = {2001},

date = {2001-02-01},

journal = {J. Biol. Chem.},

volume = {276},

number = {6},

pages = {4085--4092},

abstract = {Two novel antimicrobial peptides, which we propose to name termicin and spinigerin, have been isolated from the fungus-growing termite Pseudacanthotermes spiniger (heterometabole insect, Isoptera). Termicin is a 36-amino acid residue antifungal peptide, with six cysteines arranged in a disulfide array similar to that of insect defensins. In contrast to most insect defensins, termicin is C-terminally amidated. Spinigerin consists of 25 amino acids and is devoid of cysteines. It is active against bacteria and fungi. Termicin and spinigerin show no obvious sequence similarities with other peptides. Termicin is constitutively present in hemocyte granules and in salivary glands. The presence of termicin and spinigerin in unchallenged termites contrasts with observations in evolutionary recent insects or insects undergoing complete metamorphosis, in which antimicrobial peptides are induced in the fat body and released into the hemolymph after septic injury.},

keywords = {Amino Acid, Animals, Anti-Bacterial Agents, Antifungal Agents, Base Sequence, Chromatography, Cysteine, DNA Primers, High Pressure Liquid, hoffmann, Immunohistochemistry, Isoptera, M3i, Peptides, Protein Conformation, Recombinant Proteins, Sequence Homology},

pubstate = {published},

tppubtype = {article}

}

@article{casimir_conformational_2000,

title = {Conformational restriction of the Tyr53 side-chain in the decapeptide HE},

author = {J R Casimir and K Iterbeke and W Van Den Nest and M C Trescol-Biémont and H Dumortier and S Muller and D Gerlier and C Rabourdin-Combe and D Tourwé and J Paris},

doi = {10.1034/j.1399-3011.2000.00777.x},

issn = {1397-002X},

year  = {2000},

date = {2000-12-01},

journal = {The Journal of Peptide Research: Official Journal of the American Peptide Society},

volume = {56},

number = {6},

pages = {398--408},

abstract = {A series of conformationally restricted analogs of the hen egg lysozyme (HEL) decapeptide 52-61 in which the conformationally flexible Tyr53 residue was replaced by several more constrained tyrosine and phenylalanine analogs was prepared. Among these tyrosine and phenylalanine analogs were 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (Htc), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), 4-amino- 1,2,4,5-tetrahydro-8-hydroxy-2-benzazepine-3-one (Hba), 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one (Aba), 2-amino-6-hydroxytetralin-2-carboxylic acid (Hat) and 2-amino-5-hydroxyindan-2-carboxylic acid (Hai) in which the rotations around Calpha-Cbeta and Cbeta-Cgamma were restricted because of cyclization of the side-chain to the backbone. Synthesis of Pht-Hba-Gly-OH using a modification of the Flynn and de Laszlo procedure is described. Analogs of beta-methyltyrosine (beta-MeTyr) in which the side-chains were biased to particular side-chain torsional angles because of substitution at the beta-hydrogens were also prepared. These analogs of HEL[52-61] peptide were tested for their ability to bind to the major histocompatibility complex class II I-Ak molecule and to be recognized in this context by two T-cell hybridomas, specific for the parent peptide HEL[52-61]. The data showed that the conformation and also the configuration of the Tyr53 residue influenced both the binding of the peptide to I-Ak and the recognition of the peptide/I-Ak complex by a T-cell receptor.},

keywords = {Amino Acid Sequence, Animals, Antigen, Antigen-Presenting Cells, B-Lymphocytes, Chemical, Chickens, Dumortier, I2CT, Major Histocompatibility Complex, Mice, Models, Molecular Sequence Data, Muramidase, Peptide Biosynthesis, Peptides, Phenylalanine, Protein Binding, Protein Conformation, Receptors, T-Cell, Team-Dumortier, Temperature, Tyrosine},

pubstate = {published},

tppubtype = {article}

}

@article{cornet_refined_1995,

title = {Refined three-dimensional solution structure of insect defensin A},

author = {B Cornet and J M Bonmatin and Charles Hetru and Jules A Hoffmann and M Ptak and F Vovelle},

issn = {0969-2126},

year  = {1995},

date = {1995-05-01},

journal = {Structure},

volume = {3},

number = {5},

pages = {435--448},

abstract = {BACKGROUND: Insect defensin A is a basic 4 kDa protein secreted by Phormia terranovae larvae in response to bacterial challenges or injuries. Previous biological tests suggest that the bacterial cytoplasmic membrane is the target of defensin A. The structural study of this protein is the first step towards establishing a structure-activity relationship and forms the basis for understanding its antibiotic activity at the molecular level. RESULTS: We describe a refined model of the three-dimensional structure of defensin A derived from an extensive analysis of 786 inter-proton nuclear Overhauser effects. The backbone fold involves an N-terminal loop and an alpha-helical fragment followed by an antiparallel beta-structure. The helix and the beta-structure are connected by two of the three disulphide bridges present in defensin A, forming a so-called 'cysteine-stabilized alpha beta' (CS alpha beta) motif. The N-terminal loop, which is locally well defined, can occupy different positions with respect to the other moieties of the molecule. CONCLUSIONS: The CS alpha beta motif, which forms the core of the defensin A structure, appears to be a common organization for several families of small proteins with toxic properties. The distribution of amino acid side chains in the protein structure creates several hydrophobic or hydrophilic patches. This leads us to propose that the initial step in the action of positively charged defensin A molecules with cytoplasmic membranes may involve interactions with acidic phospholipids.},

keywords = {Amino Acid, Animals, Bacteriolysis, Chemistry, Defensins, Diptera, Gram-Positive Bacteria, hoffmann, Hydrogen Bonding, Insect Hormones, M3i, Magnetic Resonance Spectroscopy, Models, Molecular, Physical, Physicochemical Phenomena, Protein Conformation, Recombinant Proteins, Sequence Homology, Solutions, Structure-Activity Relationship},

pubstate = {published},

tppubtype = {article}

}

@article{bonmatin_two-dimensional_1992,

title = {Two-dimensional 1H NMR study of recombinant insect defensin A in water: resonance assignments, secondary structure and global folding},

author = {J M Bonmatin and J L Bonnat and X Gallet and F Vovelle and M Ptak and Jean-Marc Reichhart and Jules A Hoffmann and E Keppi and M Legrain and T Achstetter},

issn = {0925-2738},

year  = {1992},

date = {1992-01-01},

journal = {J. Biomol. NMR},

volume = {2},

number = {3},

pages = {235--256},

abstract = {A 500 MHz 2D 1H NMR study of recombinant insect defensin A is reported. This defense protein of 40 residues contains 3 disulfide bridges, is positively charged and exhibits antibacterial properties. 2D NMR maps of recombinant defensin A were fully assigned and secondary structure elements were localized. The set of NOE connectivities, 3JNH-alpha H coupling constants as well as 1H/2H exchange rates and delta delta/delta T temperature coefficients of NH protons strongly support the existence of an alpha-helix (residues 14-24) and of an antiparallel beta-sheet (residues 27-40). Models of the backbone folding were generated by using the DISMAN program and energy refined by using the AMBER program. This was done on the basis of: (i) 133 selected NOEs, (ii) 21 dihedral restraints from 3JNH-alpha H coupling constants, (iii) 12 hydrogen bonds mostly deduced from 1H/2H exchange rates or temperature coefficients, in addition to 9 initial disulfide bridge covalent constraints. The two secondary structure elements and the two bends connecting them involve approximately 70% of the total number of residues, which impose some stability in the C-terminal part of the molecule. The remaining N-terminal fragment forms a less well defined loop. This spatial organization, in which a beta-sheet is linked to an alpha-helix by two disulfide bridges and to a large loop by a third disulfide bridge, is rather similar to that found in scorpion charybdotoxin and seems to be partly present in several invertebrate toxins.},

keywords = {Animals, Defensins, hoffmann, Hydrogen, Insect Hormones, insects, M3i, Magnetic Resonance Spectroscopy, Models, Molecular, Protein Conformation, Recombinant Proteins, reichhart, Saccharomyces cerevisiae, Thermodynamics},

pubstate = {published},

tppubtype = {article}

}

@article{hetru_isolation_1991,

title = {Isolation and structural characterization of an insulin-related molecule, a predominant neuropeptide from Locusta migratoria},

author = {Charles Hetru and K W Li and Philippe Bulet and Marie Lagueux and Jules A Hoffmann},

issn = {0014-2956},

year  = {1991},

date = {1991-10-01},

journal = {Eur. J. Biochem.},

volume = {201},

number = {2},

pages = {495--499},

abstract = {Neurohaemal lobes of corpora cardiaca of Locusta migratoria are an established storage site for neurohormones produced by the neurosecretory cells of the brain. As previously reported [Hietter, H., Van Dorsselaer, A., Green, B., Denoroy, L., Hoffmann, J.A. & Luu, B. (1990) Eur. J. Biochem. 187, 241-247], the isolation and characterization of a novel 5-kDa peptide from these lobes served as the basis for oligonucleotide screening of cDNA libraries prepared from poly(A) RNA from neurosecretory cells of the central nervous system. From subsequent cDNA cloning studies [Lagueux, M., Lwoff, L., Meister, M., Goltzené, F. & Hoffmann, J.A. (1990) Eur. J. Biochem. 187, 249-254], the existence of a 145-residue precursor protein was deduced, which contained, in addition to the 5-kDa peptide, amino-acid sequences with homology to the A and B chains of an insulin-related peptide. In the present study we have isolated the native molecule from corpora cardiaca of Locusta and characterized, by Edman degradation and plasma-desorption mass spectrometry, the two chains as follows: A chain, Gly-Val-Phe-Asp-Glu-Cys-Cys-Arg-Lys-Ser-Cys-Ser-Ile-Ser-Glu-Leu-Gln-Thr- Tyr-Cys - Gly (Ile, isoleucine); B chain, Ser-Gly-Ala-Pro-Gln-Pro-Val-Ala-Arg-Tyr-Cys-Gly-Glu-Lys-Leu-Ser-Asn-Ala- Leu-Lys - Leu-Val-Cys-Arg-Gly-Asn-Tyr-Asn-Thr-Met-Phe. Taken in conjunction with the previous cloning studies, our data lead to a clear picture of the processing of Locusta preproinsulin. They indicate that locusta corpora cardiaca contain remarkably large amounts of one single insulin form, in contrast to multiple insulin isoforms of Bombyx mori, the only other insect species from which insulin-related peptides have been isolated and characterized [Nagasawa, H., Kataoka, H., Isogai, A., Tamura, S., Suzuki, A., Mizoguchi, A., Fujiwara, Y., Suzuki, A., Takahashi, S. & Ishizaki, H. (1986) Proc. Natl Acad. Sci. USA 83, 5840-5843].},

keywords = {Animals, Chromatography, DNA, Female, Grasshoppers, High Pressure Liquid, hoffmann, Insect Hormones, Insulin, M3i, Mass Spectrometry, Neuropeptides, Proinsulin, Protein Conformation},

pubstate = {published},

tppubtype = {article}

}