Evidence for Follicle-stimulating Hormone Receptor as a Functional Trimer

Jiang, Xuliang; Fischer, David J.; Chen, Xiaoyan; McKenna, Sean D.; Liu, Heli; Sriraman, Venkataraman; Yu, Hong; Goutopoulos, Andreas; Arkinstall, Steve; He, Xiaolin

doi:10.1074/jbc.m114.549592

Cited by 95 publications

(92 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The trimerization was also observed in the crystals of LGR1 with FSH that was deglycosylated at Asn-52 in the ␣-chain (53). As the trimerization buried a large surface area of each protomer, the FSH-binding capacity of LGR1 was increased to 3-fold for the deglycosylated FSH (53).…”

Section: Divergence Of Ligand Recognition Bymentioning

confidence: 72%

“…As the trimerization buried a large surface area of each protomer, the FSH-binding capacity of LGR1 was increased to 3-fold for the deglycosylated FSH (53). Although the trimer model of LGR1 in FSH recognition could well explain some observation in biochemical and functional studies (53), the in vivo relevance of the LGR1-FSH trimerization and the actual oligomerization form in living cells still need to be determined.…”

Section: Divergence Of Ligand Recognition Bymentioning

confidence: 99%

See 1 more Smart Citation

Crystal Structure of LGR4-Rspo1 Complex

Huang

Yang

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Section: Divergence Of Ligand Recognition Bymentioning

confidence: 72%

Section: Divergence Of Ligand Recognition Bymentioning

confidence: 99%

Crystal Structure of LGR4-Rspo1 Complex

Huang

Yang

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…8A). However, FSHR has been reported to exist as dimers, trimers or small oligomers in the membrane (Guan et al, 2010, Jiang et al, 2014, Thomas et al, 2007). Accordingly, binding of FSH to one ligand binding site may affect FSH binding to a second ligand binding site, and dissociation studies seemed to provide supporting evidence (Urizar et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Production, purification, and characterization of recombinant hFSH glycoforms for functional studies

Butnev

May

et al. 2015

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Summary Previously, our laboratory demonstrated the existence of a β-subunit glycosylation-deficient human FSH glycoform, hFSH21. A third variant, hFSH18, has recently been detected in FSH glycoforms isolated from purified pituitary hLH preparations. Human FSH21 abundance in individual female pituitaries progressively decreased with increasing age. Hypo-glycosylated glycoform preparations are significantly more active than fully-glycosylated hFSH preparations. The purpose of this study was to produce, purify and chemically characterize both glycoform variants expressed by a mammalian cell line. Recombinant hFSH was expressed in a stable GH3 cell line and isolated from serum-free cell culture medium by sequential, hydrophobic and immunoaffinity chromatography. FSH glycoform fractions were separated by Superdex 75 gel-filtration. Western blot analysis revealed the presence of both hFSH18 and hFSH21 glycoforms in the low molecular weight fraction, however, their electrophoretic mobilities differed from those associated with the corresponding pituitary hFSH variants. Edman degradation of FSH21/18 -derived β-subunit before and after peptide-N-glycanase F digestion confirmed that it possessed a mixture of both mono-glycosylated FSHβ subunits, as both Asn7 and Asn24 were partially glycosylated. FSH receptor-binding assays confirmed our previous observations that hFSH21/18 exhibits greater receptor-binding affinity and occupies more FSH binding sites when compared to fully-glycosylated hFSH24. Thus, the age-related reduction in hypo-glycosylated hFSH significantly reduces circulating levels of FSH biological activity that may further compromise reproductive function. Taken together, the ability to express and isolate recombinant hFSH glycoforms opens the way to study functional differences between them both in vivo and in vitro.

show abstract

“…In addition, the distal half of the ECD is linked to the TMD by a region of 130 amino acids known as the ‘hinge region’. A partial crystal structure of the ‘hinge region’ of the FSHR [12] along with other mutational studies on the TSHR hinge has now clearly shown that this structural bridge undergoes conformational changes in response to ligand binding and is involved in the activation of the receptor. Hence, this region is now often referred to as the ‘signal-specific domain’ [6,13].…”

Section: Structure and Function Of The Tshrmentioning

confidence: 99%

Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies

Davies¹,

Latif²

2015

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

Introduction The thyroid-stimulating hormone receptor (TSHR) is the essential molecule for thyroid growth and thyroid hormone production. Since it is also a key autoantigen in Graves’ disease and is involved in thyroid cancer pathophysiology, the targeting of the TSHR offers a logical model for disease control. Areas covered We review the structure and function of the TSHR and the progress in both small molecule ligands and TSHR antibodies for their therapeutic potential. Expert opinion Stabilization of a preferential conformation for the TSHR by allosteric ligands and TSHR antibodies with selective modulation of the signaling pathways is now possible. These tools may be the next generation of therapeutics for controlling the pathophysiological consequences mediated by the effects of the TSHR in the thyroid and other extrathyroidal tissues.

show abstract

Evidence for Follicle-stimulating Hormone Receptor as a Functional Trimer

Cited by 95 publications

References 49 publications

Crystal Structure of LGR4-Rspo1 Complex

Crystal Structure of LGR4-Rspo1 Complex

Production, purification, and characterization of recombinant hFSH glycoforms for functional studies

Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies

Contact Info

Product

Resources

About