β-turns in proteins

Chou, Peter Y.; Fasman, Gerald D.

doi:10.1016/0022-2836(77)90094-8

Cited by 987 publications

(442 citation statements)

References 42 publications

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“…The presence of a C = O( 1) -HN(4) hydrogen bond is possible, but not necessary for stabilization of the p-turn (Chou & Fasman, 1977). More specifically, a type I p-turn is characterized by dihedral angles (&,&) = (-60",-90") and ( 4~~4~) = (-90",0") (Venkatachalam, 1968;Richardson, 1981;Rose et al, 1985;Wilmot & Thornton 1988).…”

Section: Structure Calculationsmentioning

confidence: 99%

Solution structure of Compstatin, a potent complement inhibitor

et al. 1998

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The third component of complement, C3, plays a central role in activation of the classical, alternative, and lectin pathways of complement activation. Recently, we have identified a 13-residue cyclic peptide (named Compstatin) that specifically binds to C3 and inhibits complement activation. To investigate the topology and the contribution of each critical residue to the binding of Compstatin to C3, we have now determined the solution structure using 2D NMR techniques; we have also synthesized substitution analogues and used these to study the structure-function relationships involved. Finally, we have generated an ensemble of a family of solution structures of the peptide with a hybrid distance geometry-restrained simulated-annealing methodology, using distance, dihedral angle, and 3JNH.H,-~o~pling constant restraints. The Compstatin structure contained a type I p-turn comprising the segment GlnS-Asp6-Trp7-Glys. Preference for packing of the hydrophobic side chains of Val3, Val4, and Trp' was observed. The generated structure was also analyzed for consistency using NMR parameters such as NOE connectivity patterns, 3JNH.H,-~o~pling constants, and chemical shifts. Analysis of Ala substitution analogues suggested that Val3, G l d , Asp6, Trp7, and Glys contribute significantly to the inhibitory activity of the peptide. Substitution of Gly' caused a 100-fold decrease in inhibitory potency. In contrast, substitution of Val4, His', His", and Arg" resulted in minimal change in the activity. These findings indicate that specific side-chain interactions and the &turn are critical for preservation of the conformational stability of Compstatin and they might be significant for maintaining the functional activity of Compstatin.The complement system is the first line of immunological defense against foreign pathogens (Muller-Eberhard, 1992). Its activation through the classical, alternative, or lectin pathways leads to the generation of anaphylatoxic peptides C3a and C5a and formation of the C5b-9 membrane attack complex. Complement component C3 plays a central role in activation of all three pathways. Activation of C3 by complement pathway C3 convertases and its subsequent attachment to target surface leads to assembly of the membrane attack complex and ultimately to damage or lysis of the target cells (Frank & Fries, 1991). C3 is unique in that it possesses Reprint requests to:

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Section: Structure Calculationsmentioning

confidence: 99%

Solution structure of Compstatin, a potent complement inhibitor

et al. 1998

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“…There are three turns (the B-C turn (G44V), the F-G turn (G86V), and the H-I turn (G11OV)) that are type 11' containing glycine as the second residue (Chou & Fasman, 1977;Sibanda & Thornton, 1991). The glycine-to-valine mutation should almost certainly change the turn type, perhaps into the more common type I turn, yet there is little effect on stability suggesting that these turns do not greatly influence interactions between strands.…”

Section: Mutations In Type Ii' Turnsmentioning

confidence: 99%

Turn scanning by site‐directed mutagenesis: Application to the protein folding problem using the intestinal fatty acid binding protein

Kim

Frieden

1998

Protein Science

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We have systematically mutated residues located in turns between P-strands of the intestinal fatty acid binding protein (IFABP), and a glycine in a half turn, to valine and have examined the stability, refolding rate constants and ligand dissociation constants for each mutant protein. IFABP is an almost all P-sheet protein exhibiting a topology comprised of two five-stranded sheets surrounding a large cavity into which the fatty acid ligand binds. A glycine residue is located in seven of the eight turns between the antiparallel P-strands and another in a half turn of a strand connecting the front and back sheets. Mutations in any of the three turns connecting the last four C-terminal strands slow the folding and decrease stability with the mutation between the last two strands slowing folding dramatically. These data suggest that interactions between the last four C-terminal strands are highly cooperative, perhaps triggered by an initial hydrophobic collapse. We suggest that this trigger is collapse of the highly hydrophobic cluster of amino acids in the D and E strands, a region previously shown to also affect the last stage of the folding process . Changing the glycine in the strand between the front and back sheets also results in a unstable, slow folding protein perhaps disrupting the D-E strand interactions. For most of the other turn mutations there was no apparent correlation between stability and refolding rate constants. In some turns, the interaction between strands, rather than the turn type, appears to be critical for folding while in others, turn formation itself appears to be a rate limiting step. Although there is no simple correlation between turn formation and folding kinetics, we propose that turn scanning by mutagenesis will be a useful tool for issues related to protein folding.Keywords: P-sheet protein folding and stability; fatty acid binding; turn mutationsThe intestinal fatty acid binding protein (IFABP) is a small (15,000 Da) monomeric protein that belongs to a class of proteins that are primarily P-sheet and bind a diverse group of ligands (fatty acids, retinoids, and bile salts) into a large central cavity in the interior of the protein. The structure of the protein has been examined both by X-ray Sacchettini & Gordon, 1993;Banaszak et al., 1994) and NMR (Hodsdon et al., 1996;Hodsdon & Cistola, 1997a, 1997bZhang et al., 1997) methods. It is an excellent model protein for folding studies, not only because of its small size and P-sheet structure, but also because it contains no cysteine or proline residues. In a previous paper , we investigated the role of the turn between two antiparallel Reprint requests to: C. Frieden, Department of Biochemistry and Molecular Biophysics, Box 8231, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63 I 1 0 e-mail: frieden@biochem. wustl.edu.Abbreviutions: IFABP, rat intestinal fatty acid binding protein; Gdn, guanidine hydrochloride; EDTA, ethylenediamine tetraacetic acid; DAUDA, 1 1 -((5-dimethylaminonaphth...

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“…Secondary structure predictions (Chou & Fasman, 1974) from the amino acid sequences indicate that contiguous &turn conformations are preferred for F4-6, FCSer, F4-Asn and, to a lesser extent, F4-~-Ala (not illustrated). The torsional angles defining P-turns (Chou & Fasman, 1977) and a-helices are similar such that small distortions of the dihedral angles in turns can approach angles that define an aL-helix, a more probable conformation for an extended structure. Also, 0-turn-like conformations have been proposed to be helix precursors during the folding process (Dyson et al, 1988;Perczel et al, 1992) further emphasizing the close relationship between these two structures.…”

Section: Discussionmentioning

confidence: 99%

Structure of synthetic peptide analogues of an eggshell protein of Schistosoma mansoni

et al. 1993

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The peptide (Gly-L-Tyr-L-Asp-L-Lys-L-Tyr),, referred to as F4-6, was synthesized as a model for a schistosome eggshell protein in which the Gly-Tyr-Asp-Lys-Tyr consensus sequence is repeated over 40 times. Analysis by CD, Fourier transform infrared spectroscopy, potentiometric and spectrophotometric titrations, NMR, and molecular modeling suggests that F4-6 forms some type of left-handed structure. A likely possibility appears to be a lefthanded a-helix stabilized by Lysj-Aspj+, salt bridges and possibly Aspj-Tyrj+, hydrogen bonding and Tyr-Tyr interactions. Spectroscopic studies of a number of F4-6 analogues support this conclusion. For example, substitution of D-Ala for Gly produces a peptide with enhanced left-handed helical spectral characteristics, whereas an L-Ala substitution results in a peptide with minimal structure. These studies suggest that the F4 protein from Schistosoma mansoni may be the first example of a naturally occurring protein devoid of proline and carbohydrate that forms a left-handed helix composed of L-amino acids, although alternative forms of other left-handed structures have yet to be rigorously excluded.Keywords: F4-6 peptide; Schistosoma mansoni; schistosome eggshell protein The pathology of schistosomiasis is due to the inflammatory response to the eggs of the parasitic trematode, Schistosoma mansoni (or other closely related schistosomes) lodged in the hosts' body tissues. Granulomas form around the eggs in response to soluble carbohydrate and protein antigens secreted by the eggs. When an egg is deposited by the female schistosome, it contains a fertilized ovum and 30-40 vitelline cells. Development of the miracidium larva occurs inside the eggshell lodged in the host tissues. The eggshell is formed shortly before egg laying from protein precursors secreted by the vitelline cells that subsequently become surrounded by the eggshell. These vitelline cells serve as a food supply for the developing miracidium and disappear before hatching. The secreted

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β-turns in proteins

Cited by 987 publications

References 42 publications

Solution structure of Compstatin, a potent complement inhibitor

Solution structure of Compstatin, a potent complement inhibitor

Turn scanning by site‐directed mutagenesis: Application to the protein folding problem using the intestinal fatty acid binding protein

Structure of synthetic peptide analogues of an eggshell protein of Schistosoma mansoni

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