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Home Ο ρόλος του δεύτερου εξωκυτταρίου βρόγχου του τύπου 1 υποδοχέα του εκλυτικού παράγοντα της κορτικοτροπίνης στη λειτουργία του

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Identifier

000404402

Title

Ο ρόλος του δεύτερου εξωκυτταρίου βρόγχου του τύπου 1 υποδοχέα του εκλυτικού παράγοντα της κορτικοτροπίνης στη λειτουργία του

Alternative Title

The role of the second extracellular of type 1 receptor of the CRF in its function

Author

Αθανασάκης, Ανδρέας

Thesis advisor

Λιαπάκης, Γεώργιος

Reviewer

Μαργιωρής, Ανδρέας
Βενυχάκη, Μαρία

Abstract

Corticotrophin releasing factor (CRF) is a 41 amino acid peptide that plays important role in the function of the hypothalamic-pituitary-adrenal (HPA) axis and the central nervous system (CNS), by interacting mostly with the type 1 receptor of CRF (CRF1R). CRF1R belongs to the subfamily B of G-protein coupled receptors (GPCRs) family. CRF1R, like all GPCRs, consists of seven transmembrane domains (TM1-TM7) which are extracellularly linked ro each other by three loops (EL1-EL3). Previous studies have shown that mutation of arginine or lysine of secretin receptor and GLP1R, which corresponds to lysine 250 of CRF1R, significantly reduced the binding affinities of peptides. Similarly, replacement of lysine 250 of CRF1R by an unnatural photocrosslinking amino acid (Azi), reduced the binding affinity of the CRF related peptide, urocortin. Moreover, the existence of a positively charge at position 250 of all subfamily B GPCRs suggests its possible important role in the structure and function of receptors. All above lead to the hypothesis that Lys250 of CRF1R plays important role in receptor function. The aim of the present study is to verify the above hypothesis. To accomplish this we mutated Lys250 of CRF1R to different amino acids and tested the impact of mutations on binding affinity of the CRF related peptide, sauvagine. In specific, we mutated Lys250 to the negatively charged Asp (K250D) or to the positively charged Arg (K250R). K250D mutation drammatically reduced sauvagine binding, whereas K250R mutation had a much smaller impact on peptide binding. These results suggest that the positive charge at position 250 of CRF1R plays important role in ligand binding.

Language

Greek

Issue date

2016-12-13

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses

Type of Work--Post-graduate theses

Views

180

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