Folding studies on the human chorionic gonadotropin β-subunit using optical spectroscopy of peptide fragments

R. A. Gangani, D. Silva, Simon A. Sherman, Fulvio Perini, Elliott Bedows, Timothy A. Keiderling

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Conformational preferences for the peptides SRPINATLAVEKEGSPVSITVNTTISA (H1) and APTMTRVLQGVLPALPQVVCNYR (H2) corresponding to the amino acid residues 9-35 and 38-60, respectively, of the glycoprotein hormone human chorionic gonadotropin β-subunit (hCGβ) were studied by Fourier transform infrared spectroscopy (FTIR) and vibrational and electronic circular dichroism (VCD and ECD) in various environments. These peptides correspond to the H1 (β-like) and H2 (loop) hairpins of the native-state hCGβ subunit defined by X-ray analysis. As demonstrated by FTIR and VCD, the H1 peptide adopts a β-structure in water as well as in environments that normally induce α-helix formation, such as mixed trifluoroethanol/H2O solvent or micellar concentrations of sodium dodecyl sulfate. By contrast, the H2 peptide ECD and VCD spectra are consistent with a significant fraction of the residues being in either a poly-L-proline II like or a partially helical conformation depending on the environment. A third peptide, H3, corresponding to the 60-87 hairpin region of hCGβ, which was studied previously, switches its conformation depending on both the solvent and peptide concentration. Taken together, the data suggest that hCGβ may fold by, first, the H1 region rapidly adopting a β-hairpin structure, followed by its hydrophobic collapse with the H3 region, which in turn facilitates the formation of the H3 β-hairpin. The H2 hairpin loop is formed as a result of the formation of the H1 and H3 β-hairpin interactions.

Original languageEnglish (US)
Pages (from-to)8623-8630
Number of pages8
JournalJournal of the American Chemical Society
Volume122
Issue number36
DOIs
StatePublished - Sep 13 2000

Fingerprint

Peptide Fragments
Chorionic Gonadotropin
Peptides
Spectrum Analysis
Fourier Transform Infrared Spectroscopy
Fourier transform infrared spectroscopy
Conformations
Trifluoroethanol
Glycoproteins
Hormones
X ray analysis
Dichroism
Sodium dodecyl sulfate
Circular Dichroism
Sodium Dodecyl Sulfate
Optical spectroscopy
Gonadotropins
Amino acids
Switches
X-Rays

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Folding studies on the human chorionic gonadotropin β-subunit using optical spectroscopy of peptide fragments. / Gangani, R. A.; Silva, D.; Sherman, Simon A.; Perini, Fulvio; Bedows, Elliott; Keiderling, Timothy A.

In: Journal of the American Chemical Society, Vol. 122, No. 36, 13.09.2000, p. 8623-8630.

Research output: Contribution to journalArticle

Gangani, R. A. ; Silva, D. ; Sherman, Simon A. ; Perini, Fulvio ; Bedows, Elliott ; Keiderling, Timothy A. / Folding studies on the human chorionic gonadotropin β-subunit using optical spectroscopy of peptide fragments. In: Journal of the American Chemical Society. 2000 ; Vol. 122, No. 36. pp. 8623-8630.
@article{8c959ba612574c9abf8616952e24720a,
title = "Folding studies on the human chorionic gonadotropin β-subunit using optical spectroscopy of peptide fragments",
abstract = "Conformational preferences for the peptides SRPINATLAVEKEGSPVSITVNTTISA (H1) and APTMTRVLQGVLPALPQVVCNYR (H2) corresponding to the amino acid residues 9-35 and 38-60, respectively, of the glycoprotein hormone human chorionic gonadotropin β-subunit (hCGβ) were studied by Fourier transform infrared spectroscopy (FTIR) and vibrational and electronic circular dichroism (VCD and ECD) in various environments. These peptides correspond to the H1 (β-like) and H2 (loop) hairpins of the native-state hCGβ subunit defined by X-ray analysis. As demonstrated by FTIR and VCD, the H1 peptide adopts a β-structure in water as well as in environments that normally induce α-helix formation, such as mixed trifluoroethanol/H2O solvent or micellar concentrations of sodium dodecyl sulfate. By contrast, the H2 peptide ECD and VCD spectra are consistent with a significant fraction of the residues being in either a poly-L-proline II like or a partially helical conformation depending on the environment. A third peptide, H3, corresponding to the 60-87 hairpin region of hCGβ, which was studied previously, switches its conformation depending on both the solvent and peptide concentration. Taken together, the data suggest that hCGβ may fold by, first, the H1 region rapidly adopting a β-hairpin structure, followed by its hydrophobic collapse with the H3 region, which in turn facilitates the formation of the H3 β-hairpin. The H2 hairpin loop is formed as a result of the formation of the H1 and H3 β-hairpin interactions.",
author = "Gangani, {R. A.} and D. Silva and Sherman, {Simon A.} and Fulvio Perini and Elliott Bedows and Keiderling, {Timothy A.}",
year = "2000",
month = "9",
day = "13",
doi = "10.1021/ja0013172",
language = "English (US)",
volume = "122",
pages = "8623--8630",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "36",

}

TY - JOUR

T1 - Folding studies on the human chorionic gonadotropin β-subunit using optical spectroscopy of peptide fragments

AU - Gangani, R. A.

AU - Silva, D.

AU - Sherman, Simon A.

AU - Perini, Fulvio

AU - Bedows, Elliott

AU - Keiderling, Timothy A.

PY - 2000/9/13

Y1 - 2000/9/13

N2 - Conformational preferences for the peptides SRPINATLAVEKEGSPVSITVNTTISA (H1) and APTMTRVLQGVLPALPQVVCNYR (H2) corresponding to the amino acid residues 9-35 and 38-60, respectively, of the glycoprotein hormone human chorionic gonadotropin β-subunit (hCGβ) were studied by Fourier transform infrared spectroscopy (FTIR) and vibrational and electronic circular dichroism (VCD and ECD) in various environments. These peptides correspond to the H1 (β-like) and H2 (loop) hairpins of the native-state hCGβ subunit defined by X-ray analysis. As demonstrated by FTIR and VCD, the H1 peptide adopts a β-structure in water as well as in environments that normally induce α-helix formation, such as mixed trifluoroethanol/H2O solvent or micellar concentrations of sodium dodecyl sulfate. By contrast, the H2 peptide ECD and VCD spectra are consistent with a significant fraction of the residues being in either a poly-L-proline II like or a partially helical conformation depending on the environment. A third peptide, H3, corresponding to the 60-87 hairpin region of hCGβ, which was studied previously, switches its conformation depending on both the solvent and peptide concentration. Taken together, the data suggest that hCGβ may fold by, first, the H1 region rapidly adopting a β-hairpin structure, followed by its hydrophobic collapse with the H3 region, which in turn facilitates the formation of the H3 β-hairpin. The H2 hairpin loop is formed as a result of the formation of the H1 and H3 β-hairpin interactions.

AB - Conformational preferences for the peptides SRPINATLAVEKEGSPVSITVNTTISA (H1) and APTMTRVLQGVLPALPQVVCNYR (H2) corresponding to the amino acid residues 9-35 and 38-60, respectively, of the glycoprotein hormone human chorionic gonadotropin β-subunit (hCGβ) were studied by Fourier transform infrared spectroscopy (FTIR) and vibrational and electronic circular dichroism (VCD and ECD) in various environments. These peptides correspond to the H1 (β-like) and H2 (loop) hairpins of the native-state hCGβ subunit defined by X-ray analysis. As demonstrated by FTIR and VCD, the H1 peptide adopts a β-structure in water as well as in environments that normally induce α-helix formation, such as mixed trifluoroethanol/H2O solvent or micellar concentrations of sodium dodecyl sulfate. By contrast, the H2 peptide ECD and VCD spectra are consistent with a significant fraction of the residues being in either a poly-L-proline II like or a partially helical conformation depending on the environment. A third peptide, H3, corresponding to the 60-87 hairpin region of hCGβ, which was studied previously, switches its conformation depending on both the solvent and peptide concentration. Taken together, the data suggest that hCGβ may fold by, first, the H1 region rapidly adopting a β-hairpin structure, followed by its hydrophobic collapse with the H3 region, which in turn facilitates the formation of the H3 β-hairpin. The H2 hairpin loop is formed as a result of the formation of the H1 and H3 β-hairpin interactions.

UR - http://www.scopus.com/inward/record.url?scp=0034644437&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034644437&partnerID=8YFLogxK

U2 - 10.1021/ja0013172

DO - 10.1021/ja0013172

M3 - Article

AN - SCOPUS:0034644437

VL - 122

SP - 8623

EP - 8630

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 36

ER -