Linked Life Data

8672495

Source:http://linkedlifedata.com/resource/pubmed/id/8672495

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
1996-8-15
pubmed:abstractText
Follicle-stimulating hormone (FSH) is in the family of pituitary/placental glycoprotein hormones which also includes luteinizing hormone (LH), chorionic gonadotropin (hCG), and thyroid-stimulating hormone. These hormones are heterodimers composed of common alpha- and similar but unique beta-subunits. The 21 amino acid loop between Y33 and F53 of the FSH beta-subunit (L2 beta) can be switched into L2 beta of hCG beta without a loss of receptor binding, yet mutation of hFSH beta 37LVY39 to 37AAA39 was antecendent to a 20-fold reduction in receptor binding (based on ID50). A mutation in the LH beta gene, which causes Q54 to be R, causes hypogonadism. This residue is conserved in the glycoprotein hormones and corresponds to Q48 in hFSH beta. Mutation of hFSH beta 48QKTCT52 to 48AAACA52 resulted in a failure of heterodimer formation. In the current study single mutations were made to pinpoint which of the seven hFSH beta residues in the 37LVY39 to 37AAA39 and the 48QKTCT52 to 48AAACA52 mutants were responsible for the observed phenotypes. A single mutation of T52 to alanine was sufficient to cause a reduction in expression of heterodimeric hormone. Single mutants Q48A, T50A, V38A, Y39A, and, to a lesser extent, T52A formed heterodimer. However, these hFSH mutants were markedly unstable at pH 2.0. Thus, acid dissociation can be used to reveal metastable forms of this protein. Mutant hFSH beta Q48A was also 8-fold less active than wild-type hFSH when assayed for binding to hFSH receptors. hFSH beta V38A and Y39A mutants affected receptor binding; however, neither mutation alone caused greater than a 2-fold decrease in receptor binding activity. In summary, these results identify single important residues in the long loop (between Y33 and F53) of the hFSH beta-subunit which are required for proper subunit interactions that provide conformational stability which in turn is necessary for FSH-receptor interaction.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7928-35
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8672495-Amino Acid Sequence, pubmed-meshheading:8672495-Animals, pubmed-meshheading:8672495-Base Sequence, pubmed-meshheading:8672495-Calorimetry, pubmed-meshheading:8672495-Cell Line, pubmed-meshheading:8672495-Circular Dichroism, pubmed-meshheading:8672495-DNA, Complementary, pubmed-meshheading:8672495-Follicle Stimulating Hormone, pubmed-meshheading:8672495-Follicle Stimulating Hormone, beta Subunit, pubmed-meshheading:8672495-Humans, pubmed-meshheading:8672495-Kinetics, pubmed-meshheading:8672495-Macromolecular Substances, pubmed-meshheading:8672495-Molecular Sequence Data, pubmed-meshheading:8672495-Mutagenesis, Site-Directed, pubmed-meshheading:8672495-Oligodeoxyribonucleotides, pubmed-meshheading:8672495-Point Mutation, pubmed-meshheading:8672495-Protein Conformation, pubmed-meshheading:8672495-Protein Structure, Secondary, pubmed-meshheading:8672495-Receptors, FSH, pubmed-meshheading:8672495-Recombinant Proteins, pubmed-meshheading:8672495-Spodoptera, pubmed-meshheading:8672495-Thermodynamics, pubmed-meshheading:8672495-Transfection
pubmed:year
1996
pubmed:articleTitle
Follitropin conformational stability mediated by loop 2 beta effects follitropin-receptor interaction.
pubmed:affiliation
Wadsworth Center, Division of Genetic Disorders, Laboratory of Reproductive and Metabolic Disorders, Albany, New York 12201-0509, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.