BIOMAT Database Logo BIOMAT Database Logo

Identification of amino acids in the N-terminal domain of corticotropin-releasing factor receptor 1 that are important determinants of high-affinity ligand binding. 1999

S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Department of Molecular Neuroendocrinology, Max-Planck Institute for Experimental Medicine, Göttingen, Germany.

The aim of the present study was to identify the N-terminal regions of human corticotropin-releasing factor (CRF) receptor type 1 (hCRF-R1) that are crucial for ligand binding. Mutant receptors were constructed by replacing specific residues in hCRF-R1 with amino acids from the corresponding position in the N-terminal region of the human vasoactive intestinal peptide receptor type 2 (hVIP-R2). In cyclic AMP stimulation and CRF binding assays, it was established that two regions within the N-terminal domain were crucial for the binding of CRF receptor agonists and antagonists: one region mapping to amino acids 43-50 and a second amino acid sequence extending from position 76 to 84 of hCRF-R1. Recently, it was found that the latter sequence plays a very important role in determining the high ligand selectivity of the Xenopus CRF-R1 (xCRF-R1). Replacement of amino acids 76-84 of hCRF-R1 with residues from the same segment of the hVIP-R2 N terminus markedly reduced the binding affinity of CRF ligands. Mutation of Arg76 or Asn81 but not Gly83 of hCRF-R1 to the corresponding amino acids of xCRF-R1 or hVIP-R2 resulted in 100-1,000-fold lower affinities for human/rat CRF, rat urocortin, and astressin. These data underline the importance of the N-terminal domain of CRF-R1 in high-affinity ligand binding.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003346 Corticotropin-Releasing Hormone A peptide of about 41 amino acids that stimulates the release of ADRENOCORTICOTROPIC HORMONE. CRH is synthesized by neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, CRH stimulates the release of ACTH from the PITUITARY GLAND. CRH can also be synthesized in other tissues, such as PLACENTA; ADRENAL MEDULLA; and TESTIS. ACTH-Releasing Hormone,CRF-41,Corticotropin-Releasing Factor,Corticotropin-Releasing Hormone-41,ACTH-Releasing Factor,CRF (ACTH),Corticoliberin,Corticotropin-Releasing Factor-41,ACTH Releasing Factor,ACTH Releasing Hormone,Corticotropin Releasing Factor,Corticotropin Releasing Factor 41,Corticotropin Releasing Hormone,Corticotropin Releasing Hormone 41
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000596 Amino Acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Amino Acid,Acid, Amino,Acids, Amino
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Identification of four amino acids in the gastrin-releasing peptide receptor that are required for high affinity agonist binding.
July 1997, The Journal of biological chemistry,
S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Binding differences of human and amphibian corticotropin-releasing factor type 1 (CRF(1)) receptors: identification of amino acids mediating high-affinity astressin binding and functional antagonism.
May 2004, Regulatory peptides,
S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Impact of N-terminal domains for corticotropin-releasing factor (CRF) receptor-ligand interactions.
February 2005, Biochemistry,
S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Identification of amino acids in the N-terminal SH2 domain of phospholipase C gamma 1 important in the interaction with epidermal growth factor receptor.
December 1994, Biochemistry,
S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Functional and protein chemical characterization of the N-terminal domain of the rat corticotropin-releasing factor receptor 1.
October 2001, Protein science : a publication of the Protein Society,
S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Juxtamembrane region of the amino terminus of the corticotropin releasing factor receptor type 1 is important for ligand interaction.
February 2001, Biochemistry,
S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
The role of the fourth extracellular domain of the rat corticotropin-releasing factor receptor type 1 in ligand binding.
January 1999, European journal of biochemistry,
S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Mapping of the ligand-selective domain of the Xenopus laevis corticotropin-releasing factor receptor 1: implications for the ligand-binding site.
April 1998, Proceedings of the National Academy of Sciences of the United States of America,
S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Determinants of corticotropin releasing factor. Receptor selectivity of corticotropin releasing factor related peptides.
June 2004, Journal of medicinal chemistry,
S Wille, and S Sydow, and M R Palchaudhuri, and J Spiess, and F M Dautzenberg
Dimerization of corticotropin-releasing factor receptor type 1 is not coupled to ligand binding.
January 2005, Journal of receptor and signal transduction research,
Copied contents to your clipboard!