1fl7 | pdb_00001fl7
HUMAN FOLLICLE STIMULATING HORMONE
Structural highlights
Disease[FSHB_HUMAN] Defects in FSHB are a cause of isolated follicle-stimulating hormone deficiency (IFSHD) [MIM:229070]. Selective follicle-stimulating hormone deficiency is an uncommon cause of infertility, producing amenorrhea and hypogonadism in women and oligo or azoospermia with normal testosterone levels in normally virilised men.[1] [2] [3] Function[FSHB_HUMAN] Stimulates development of follicle and spermatogenesis in the reproductive organs. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe crystal structure of a betaThr26Ala mutant of human follicle-stimulating hormone (hFSH) has been determined to 3.0 A resolution. The hFSH mutant was expressed in baculovirus-infected Hi5 insect cells and purified by affinity chromatography, using a betahFSH-specific monoclonal antibody. The betaThr26Ala mutation results in elimination of the betaAsn24 glycosylation site, yielding protein more suitable for crystallization without affecting the receptor binding and signal transduction activity of the glycohormone. The crystal structure has two independent hFSH molecules in the asymmetric unit and a solvent content of about 80%. The alpha- and betasubunits of hFSH have similar folds, consisting of central cystine-knot motifs from which three beta-hairpins extend. The two subunits associate very tightly in a head-to-tail arrangement, forming an elongated, slightly curved structure, similar to that of human chorionic gonadotropin (hCG). The hFSH heterodimers differ only in the conformations of the amino and carboxy termini and the second loop of the beta-subunit (L2beta). Detailed comparison of the structures of hFSH and hCG reveals several differences in the beta-subunits that may be important with respect to receptor binding specificity or signal transduction. These differences include conformational changes and/or differential distributions of polar or charged residues in loops L3beta (hFSH residues 62-73), the cystine noose, or determinant loop (residues 87-94), and the carboxy-terminal loop (residues 94-104). An additional interesting feature of the hFSH structure is an extensive hydrophobic patch in the area formed by loops alphaL1, alphaL3, and betaL2. Glycosylation at alphaAsn52 is well known to be required for full signal transduction activity and heterodimer stability. The structure reveals an intersubunit hydrogen bonding interaction between this carbohydrate and betaTyr58, an indication of a mechanism by which the carbohydrate may stabilize the heterodimer. Three-dimensional structure of human follicle-stimulating hormone.,Fox KM, Dias JA, Van Roey P Mol Endocrinol. 2001 Mar;15(3):378-89. PMID:11222739[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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