Dino Moras, Research Director at the CNRS, graduated in chemistry at the U. Louis Pasteur in Strasbourg where he prepared his PhD. In 1973 he joined the laboratory of M.G. Rossmann at Purdue U. for a post-doctoral stay. He contributed to the discovery of the nucleotide binding domain known as the 'Rossmann fold'. Back to Strasbourg he started the first of his two main biological projects, both related to the expression of the genetic information. In 1980, he created the biological crystallography laboratory at the IBMC of CNRS. In 1994, with his team he joined the newly created Institute of Genetics and Molecular biology (IGBMC) in Illkirch near Strasbourg.
Main Scientific contributions:
A - Translation of the genetic code
Structure-function relationships in transfer RNAs (tRNAs) and aminoacyl-tRNA synthetases and their relation to the origin of the genetic code. (i) the partition of aaRS in two classes, based on structural and functional correlations, (ii) the first structure determination of a class II complex and (iii) the elucidation of the mechanism of aminoacylation in the aspartic acid system.
He also elucidated another important problem related to the fidelity of the translation of the genetic code: the solution of the Pauling paradox in the case of threonine. He unravelled the molecular mechanism of the editing reaction to correct for tRNA mischarging by serine.
B - Transcription regulation by Nuclear Hormones Receptors (NRs)
NRs constitute a superfamily of ligand-dependent transcription factors that regulate the expression of important target genes. They play an important role in most physiological functions and are implicated in pathological processes such as cancer, diabetes and cardiovascular diseases.
In 1995 Dino Moras solved the first crystal structures of the ligand binding domains of two nuclear receptors (NRs) of retinoids (RXR and RAR) in their apo and liganded form respectively. These discoveries allowed for the first time to see these molecules and understand their mode of action at the atomic level. The structures revealed the molecular mechanism of ligand dependent activation and set up the bases for the design of agonist and antagonist drugs. The structure of the NR of vitamin D in 2000 another medically important drug target, is also an highlight of his career. Discovery of two mutually exclusive signature motifs of the ligand binding domain that partition the nuclear receptor superfamily into two classes with specific molecular pathways.
The structural basis for understanding the role of DNA in the spatial organization of NHR heterodimers in functional transcription complexes with cofactors has been investigated using a combination of solution techniques. Several structures have been determined.