Data Sciences and Brain Health across the Life Course session in 2020 SICSA Conference Oct 01, 2020 01:15 PM - 03:15 PM — Virtual Meeting (online)
Ophthalmic Medical Image Analysis MICCAI 2020 Workshop Oct 08, 2020 12:00 AM — Virtual Meeting (online)
Predictive Intelligence in Medicine MICCAI 2020 Workshop Oct 08, 2020 12:00 AM — Virtual Meeting (online)
PET is Wonderful Annual Meeting 2020 Oct 27, 2020 02:00 PM - 05:40 PM — Virtual Meeting (online)

eLearning

SINAPSE experts from around Scotland have developed ten online modules designed to explain medical imaging. They are freely available and are intended for non-specialists.


Edinburgh Imaging Academy at the University of Edinburgh offers the following online programmes through a virtual learning environment:

Neuroimaging for Research MSc/Dip/Cert

Imaging MSc/Dip/Cert

PET-MR Principles & Applications Cert

Applied Medical Image Analysis Cert

Online Short Courses

Evolution of constrained gonadotropin-releasing hormone ligand conformation and receptor selectivity

Author(s): P. E. Barran, R. W. Roeseke, A. J. Pawson, R. Sellar, M. T. Bowers, K. Morgan, Z. L. Lu, M. Tsuda, T. Kusakabe, R. P. Millar

Abstract:
Gonadotropin-releasing hormone (GnRH) is the central regulator of reproduction in vertebrates. GnRHs have recently been identified in protochordates and retain the conserved N- and C-terminal domains involved in receptor binding and activation. GnRHs of the jawed vertebrates have a central achiral amino acid (glycine) that favors a type II' beta-turn such that the N- and C-terminal domains are closely apposed in binding the GnRH receptor. However, protochordate GnRHs have a chiral amino acid in this position, suggesting that they bind their receptors in a more extended form. We demonstrate here that a protochordate GnRH receptor does not distinguish GnRHs with achiral or chiral amino acids, whereas GnRH receptors of jawed vertebrates are highly selective for GnRHs with the central achiral glycine. The poor activity of the protochordate GnRH was increased >10-fold at vertebrate receptors by replacement of the chiral amino acid with glycine or a D-amino acid, which favor the type II' beta-turn. Structural analysis of the GnRHs using ion mobility-mass spectrometry and molecular modeling showed a greater propensity for a type II' beta-turn in GnRHs with glycine or a D-amino acid, which correlates with binding affinity at vertebrate receptors. These findings indicate that the substitution of glycine for a chiral amino acid in GnRH during evolution allows a more constrained conformation for receptor binding and that this subtle single amino acid substitution in a site remote from the ligand functional domains has marked effects on its structure and activity.

Full version: Available here

Click the link to go to an external website with the full version of the paper


ISBN: 0021-9258
Publication Year: 2005
Periodical: Journal of Biological Chemistry
Periodical Number: 46
Volume: 280
Pages: 38569-38575
Author Address: