Growth hormone conformation and conformational equilibriums

La, Holladay; Hammonds, R. Glenn; Puett, David

doi:10.1021/bi00705a015

Cited by 91 publications

(86 citation statements)

References 57 publications

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“…2, the changes in [6] at 242 nm and 225 nm are very nearly coincident as the denaturant concentration is increased to 6 M. Moreover, the major portion of the spectral changes occurs between 2 M and 4 M GdmCl and has the appearance of a cooperative-like transition (11). Based on an analogy with other proteins (21), the conformation of somatostatin should be more disordered in concentrated GdmCl.…”

Section: Resultsmentioning

confidence: 91%

“…However, no studies have appeared on the conformational aspects of somatostatin. Our laboratory has been engaged in a number of studies aimed at elucidating more quantitatively the contributions of the aromatic and disulfide chromophores to the circular dichroism spectra of proteins, hormones, and fragments (10)(11)(12)(13)(14)(15). Similar studies on somatostatin, which are described herein, have led us to conclude that this tetradecapeptide exhibits a stable intramolecular struc- Amino-acid analyses were done on 100-300 tig amounts of reduced (dithiothreitol in 6 M GdmCl), S-carboxymethylated (iodoacetate) somatostatin hydrolyzed in 0.6 ml of 4 M methanesulfonic acid containing 0.2% of 3-(2-aminoethyl)-indole for 22 hr at 1150 (16).…”

mentioning

confidence: 99%

“…The cell was maintained at a constant set temperature using a thermostatted cell block and a circulating water bath. Experimental protocol and data reduction were as described elsewhere (11,13,15). Unless indicated otherwise, [0] represents the mean residue ellipticity in degree-cm2/decimole and rotational strengths, R, are in cgs units.…”

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confidence: 99%

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Somatostatin conformation: evidence for a stable intramolecular structure from circular dichroism, diffusion, and sedimentation equilibrium.

Holladay¹,

Puett²

1976

Proc. Natl. Acad. Sci. U.S.A.

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Somatostatin is a hypothalamic tetradecapeptide that inhibits the release of growth hormone, insulin, and glucagon. The circular dichroism spectrum is characterized by negative extrema at 238 nm and 270 nm, and a positive extremum at 225 nm. The far ultraviolet circular dichroism spectrum is consistent with the presence of ordered secondary structure such as a-structure, but not a-helix. Sedimentation equilibrium results demonstrate that somatostatin exists in its monomeric form (i.e., a molecular weight of 1610 4 36 was obtained) and, thus, the structure must arise from intramolecular interactions. The diffusion constant of sometostatin was estimated to be 1.66 X 10-6 cm2/sec. These data are consistent with an ellipsoidal rather than a spherical shape. The magnitude of the ellipticity at both 225 nm and 238 nm is quite dependent on guanidinium hydrochloride concentration; the midpoint occurs at about 3 M and the transition is cooperative-like. These data strongly suggest that somatostatin has a stable conformation in aqueous solution. A model, consistent with the results of the physicochemical studies and with semi-empirical rules for secondary structure formation, is proposed for somatostatin. The proposed structure consists of a hairpin loop with several residues in an antiparallel a-pleated sheet, is somewhat elongated, and contains a hydrophobic domain at one end and a hydrophilic domain at the other end.

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Section: Resultsmentioning

confidence: 91%

mentioning

confidence: 99%

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Somatostatin conformation: evidence for a stable intramolecular structure from circular dichroism, diffusion, and sedimentation equilibrium.

Holladay¹,

Puett²

1976

Proc. Natl. Acad. Sci. U.S.A.

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“…The presence of stable intermediates has been demonstrated for some members of the growth hormone family (Burger et al, 1966;Holladay et al, 1974;Bastiras & Wallace, 1992;DeFelippis et al, 1995). The equilibrium unfolding of bGH has been shown to be a multistate process in which at least four species have been identified: a native, a monomeric folding intermediate, an associated folding intermediate, and an unfolded form (Brems et al, 1985Have1 et al, 1986Have1 et al, , 1988.…”

Section: Discussionmentioning

confidence: 99%

“…2A) displays minima at 221 and 209 nm, which are characteristic of proteins with high a-helix content. Other members of the growth hormone family showed similar far-UV CD spectra (Aloj & Edelhoch, 1970, 1972Holladay et al, 1974). The apparent a-helix content of native oPL was 58%, estimated according to Zhong and Johnson (1992).…”

Section: CDmentioning

confidence: 90%

Detection and characterization of an ovine placental lactogen stable intermediate in the urea‐induced unfolding process

et al. 1996

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The urea-induced equilibrium unfolding of ovine placental lactogen, purified from ovine placenta, was followed by size-exclusion chromatography, far-UV CD, and intrinsic tryptophan fluorescence. The data obtained by each of these methods showed a poor fit to a two-state model involving only a native and an unfolded form. A satisfactory fit required, instead, a model that involved a stable, partially folded form in addition to the native and unfolded ones. The results obtained from the best-fitting theoretical curves for the three-state model indicated that this intermediate state, which is the predominant species in solution at 3.6 M of urea activity, is compact, largely a-helical, and changes considerably the native-like tertiary packing around its tryptophan residues. These findings suggest that this stable intermediate exhibits properties similar to those that characterize the molten globule state.

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Circular dichroism of corticotropin, fragment 1–24, and model compounds. An assessment of the contributions of the peptide chromophore and aromatic residues

Holladay¹,

Puett²

1976

Biopolymers

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SynopsisThe far-ultraviolet circular dichroic spectrum of the 39-residue peptide hormone porcine corticotropin and the biologically active fragment corticotropin 1-24 is negative from 250 nm to 195 nm in water, but in 6M guanidinium chloride a positive band appears at about 225 nm. The temperature and guanidinium chloride dependence of this spectral transition indicates the absence of any stable ordered secondary structure in corticotropin and the spectrum is seen to be in only partial agreement with results using the model peptide chromophore, Ala-Ala-Ala. Using oligopeptides containing aromatic amino acid residues sandwiched between glycyl residues, it is shown that the shape and intensity of the corticotropin 225 nm positive band which appears in 6M guanidinium chloride is in agreement with the far-ultraviolet transitions of the aromatic chromophores in the hormone. Curve resolution of the near-ultraviolet circular dichroic spectrum of corticotropin and comparison of the rotational strengths of the phenylalanyl and tyrosyl bands reveals no evidence for increased rotational freedom in 6 M guanidinium hydrochloride. Spectral changes are observed, however, in the transitions arising from the single tryptophan. This study suggests that corticotropin in aqueous solution may serve as a better model for the circular dichroic spectrum of the aperiodic regions in globular proteins than either synthetic homopolypeptides or reference proteins for which spectral and X-ray diffraction data are available.

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Growth hormone conformation and conformational equilibriums

Cited by 91 publications

References 57 publications

Somatostatin conformation: evidence for a stable intramolecular structure from circular dichroism, diffusion, and sedimentation equilibrium.

Somatostatin conformation: evidence for a stable intramolecular structure from circular dichroism, diffusion, and sedimentation equilibrium.

Detection and characterization of an ovine placental lactogen stable intermediate in the urea‐induced unfolding process

Circular dichroism of corticotropin, fragment 1–24, and model compounds. An assessment of the contributions of the peptide chromophore and aromatic residues

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