Le jeudi 18 décembre 2025, Romain MALEMPRE présentera l'examen en vue de l’obtention du grade académique de Docteur en Sciences (Collège de doctorat en Biochimie, biologie moléculaire et cellulaire, bioinformatique et modélisation) sous la direction d'André MATAGNE et Loïc QUINTON.

Cette épreuve consistera en la défense publique d’une dissertation intitulée :

« Probing Protein Folding Pathways by Hydrogen-Deuterium Exchange. 
A Time-Resolved Study of BS3 ß-Lactamase as a Model System ».

Le Jury sera composé de :

M. M. GALLENI (Président), Mme et MM. J. BALBACH (Martin-Luther-Universität Halle-Wittenberg, Allemagne), C. DAMBLON, A. MATAGNE (Promoteur), G. MAZZUCCHELLI, C. MICHAUX (UNamur), L. QUINTON (Co-promoteur), A. VANDENBROECK (Secrétaire).

Abstract

Understanding how proteins acquire their functional conformation remains a central challenge in structural biology, particularly for multidomain proteins whose folding trajectories involve intermediates and kinetic traps. Exported enzymes translocated through the Sec system provide a relevant model: they must remain unfolded during passage across the membrane and then spontaneously refold once secretion is complete.

Within this framework, the folding of the BS3 class A β-lactamase from Bacillus licheniformis was characterized at high resolution using hydrogen–deuterium exchange, mass spectrometry and NMR. These approaches reveal a sequence of intermediates guided by an early nucleation core formed by the β4–β5 hairpin, followed by the stepwise organization of the domains and a final maturation phase limited by proline isomerizations. A cleavable variant and evolutionary analyses further show that this motif represents a conserved folding nucleus among β-lactamases and PBPs, highlighting that folding pathways are governed by interdependent rather than autonomous structural units.