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Primary and secondary structural determinants in the receptor binding sequence. beta. -(38-57) from human luteinizing hormone

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00425a010· OSTI ID:6208813
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The intercysteine loop sequence 38-57 in the ..beta.. subunit has been shown to be a determinant for expression of biological activity in human lutropin (hLH) and choriogonadotropin (hCG). Together with other sequences, the 38-57 region may contribute to a multicomponent receptor binding domain in hLH/hCG. Because the structural features influencing activity in this important region are not easy to evaluate in the full-length subunit, the authors have used analogues of hLH..beta..-(38-57) prepared by solid-phase synthesis. The peptides were tested for inhibition of /sup 125/I-labeled hCG binding to rat ovarian membrane receptors. Secondary structure was analyzed by circular dichroism (CD) and by reactivity with antibodies to the native 38-57 peptide. An analogue lacking the 38-57 disulfide linkage retained 20% receptor binding and full immunoreactivity. Far-ultraviolet CD profiles were essentially identical with those of the disulfide-intact peptide; a transition from 10% to 30% ..cap alpha..-helix in 90% trifluoroethanol was characteristic of both. The peptide thus appears not to require the disulfide bridge to retain a looped conformation with amphipathic secondary structure. An essential positive charge at position 43 was shown by complete loss of activity upon substitution of Asp or Ala for the Arg found in all known species of LH. These results indicate that the 38-57 sequence is a relatively rigid and structurally autonomous region, not merely a series of residues constrained passively into a loop by a disulfide linkage. It includes segments of ordered structure, probably including both amphipathic helical and turn sequences. Evidence from studies of other hormones suggests that this region may be important to binding and specificity in the glycoprotein hormones as a group.

Research Organization:
Massachusetts General Hospital, Boston (USA)
OSTI ID:
6208813
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:25; ISSN BICHA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
CARBOHYDRATES
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DICHROISM
ELECTROMAGNETIC RADIATION
ELECTRON CAPTURE RADIOISOTOPES
FAR ULTRAVIOLET RADIATION
GLUCOPROTEINS
GLYCOPROTEINS
GONADOTROPINS
HCG
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LH
MAMMALS
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
RADIATIONS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RATS
RECEPTORS
RODENTS
SACCHARIDES
TRACER TECHNIQUES
ULTRAVIOLET RADIATION
VERTEBRATES