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Research Resource: Novel Structural Insights Bridge Gaps in Glycoprotein Hormone Receptor Analyses
- Source :
- Molecular endocrinology, 27(8): 1357-1363
- Publication Year :
- 2013
- Publisher :
- The Endocrine Society, 2013.
-
Abstract
- The first version of a glycoprotein hormone receptor (GPHR) information resource was designed to link functional with structural GPHR information, in order to support sequence-structure-function analysis of the LH, FSH, and TSH receptors (http://ssfa-gphr.de). However, structural information on a binding- and signaling-sensitive extracellular fragment (∼100 residues), the hinge region, had been lacking. A new FSHR crystal structure of the hormone-bound extracellular domain has recently been solved. The structure comprises the leucine-rich repeat domain and most parts of the hinge region. We have not only integrated the new FSHR/FSH structure and the derived homology models of TSHR/TSH, LHCGR/CG, and LHCGR/LH into our web-based information resource, but have additionally provided novel tools to analyze the advanced structural features, with the common characteristics and distinctions between GPHRs, in a more precise manner. The hinge region with its second hormone-binding site allows us to assign functional data to the new structural features between hormone and receptor, such as binding details of a sulfated tyrosine (conserved throughout the GPHRs) extending into a pocket of the hormone. We have also implemented a protein interface analysis tool that enables the identification and visualization of extracellular contact points between interaction partners. This provides a starting point for comparing the binding patterns of GPHRs. Together with the mutagenesis data stored in the database, this will help to decipher the essential residues for ligand recognition and the molecular mechanisms of signal transduction, extending from the extracellular hormone-binding site toward the intracellular G protein-binding sites.
- Subjects :
- Models, Molecular
endocrine system
Plasma protein binding
Computational biology
Biology
Crystallography, X-Ray
Homology (biology)
Thyrotropin receptor
Endocrinology
Humans
Research Resource
Protein Interaction Domains and Motifs
Binding site
Databases, Protein
Receptor
Molecular Biology
Glycoproteins
chemistry.chemical_classification
Internet
Binding Sites
Receptors, Thyrotropin
General Medicine
Receptors, LH
hormone
signal transduction
protein binding
leucine
internet
glycoprotein hormone
thyrotropin receptor
crystal structure
information resources
hormone binding
thyrotropin
mutagenesis
tyrosine
ligands
Protein Structure, Tertiary
chemistry
Biochemistry
Hormone receptor
Receptors, FSH
Signal transduction
Glycoprotein
Subjects
Details
- ISSN :
- 19449917 and 08888809
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Molecular Endocrinology
- Accession number :
- edsair.doi.dedup.....cb88de646b60a42cc5ce086489929f4d