Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone–receptor interactions

Autor: Buckler David Rogers, Wayne A. Hendrickson, Arnaud Ythier, Michel Dreano, Hao Wu, Nabil El Tayar, Xuliang Jiang, Cheng Shirley Vui Yen
Rok vydání: 1995
Předmět:
Models
Molecular
Glycosylation
Chemical Phenomena
Swine
G-coupled receptor
Molecular Sequence Data
Thyrotropin
leucine-rich repeats
Receptors
Cell Surface
Plasma protein binding
Leucine-rich repeat
Biology
exons
Chorionic Gonadotropin
Protein Structure
Secondary
Structure-Activity Relationship
Protein structure
GTP-Binding Proteins
Structural Biology
Animals
Humans
Hormone metabolism
Amino Acid Sequence
Structural motif
Receptor
Molecular Biology
Repetitive Sequences
Nucleic Acid
Binding Sites
Sequence Homology
Amino Acid
Chemistry
Physical
Receptors
Thyrotropin
Luteinizing Hormone
Receptors
LH
Protein superfamily
ribonuclease inhibitor
Hormones
Rats
Biochemistry
Mutagenesis
Hormone receptor
Cystine
Receptors
FSH
β-barrel geometry
Follicle Stimulating Hormone
Sequence Alignment
gonadotropins
Protein Binding
Zdroj: Structure. 3:1341-1353
ISSN: 0969-2126
Popis: Background: Glycoprotein hormones influence the development and function of the ovary, testis and thyroid by binding to specific high-affinity receptors. The extracellular domains of these receptors are members of the leucine-rich repeat (LRR) protein superfamily and are responsible for the high-affinity binding. The crystal structure of a glycoprotein hormone, namely human choriogonadotropin (hCG), is known, but neither the receptor structure, mode of hormone binding, nor mechanism for activation, have been established. Results Despite very low sequence similarity between exon-demarcated LRRs in the receptors and the LRRs of porcine ribonuclease inhibitor (RI), the secondary structures for the two repeat sets are found to be alike. Constraints on curvature and β -barrel geometry from the sequence pattern for repeated β α units suggest that the receptors contain three-dimensional structures similar to that of RI. With the RI crystal structure as a template, models were constructed for exons 2–8 of the receptors. The model for this portion of the choriogonadotropin receptor is complementary in shape and electrostatic characteristics to the surface of hCG at an identified focus of hormone–receptor interaction. Conclusion The predicted models for the structures and mode of hormone binding of the glycoprotein hormone receptors are to a large extent consistent with currently available biochemical and mutational data. Repeated sequences in β -barrel proteins are shown to have general implications for constraints on structure. Averaging techniques used here to recognize the structural motif in these receptors should also apply to other proteins with repeated sequences.
Databáze: OpenAIRE
Externí odkaz: