Researchers comment on two recent Nature Communications publications on enzyme complexes involved in collagen glycosylation, discussing how these findings lay a foundation for understanding collagen I...

Collagen IV, an essential and evolutionarily conserved component of basement membranes, is one of the most extensively post-translationally modified p…

Hydroxylysine galactosylation is essential for collagen maturation. This work reveals the molecular structure of human GLT25D1, its catalytic residues, and a noncatalytic structural domain stabilized ...

In una manifestazione promossa da Coldiretti, principale organizzazione degli imprenditori agricoli italiani, che si è svolta mercoledì 19 marzo a Parma, si sono radunate, secondo gli organizzatori, 2...

Si tratta dei progetti di ricerca di Riccardo Piccinno e di Giovanni Stelitano, che studieranno rispettivamente un batterio che vive ospite nel moscerino dei piccoli frutti e lo sviluppo di nuovi antimicrobici per combattere patogeni opportunisti.

During biosynthesis, collagen lysine residues undergo extensive post-translational modifications essential for the stability and functions of collagen supramolecular assemblies. In the endoplasmic reticulum, two distinct metal ion dependent enzyme families (i.e., multifunctional lysyl hydroxylases-glucosyltransferases LH/PLODs and galactosyltransferases GLT25D/COLGALT) alternatively operate on collagen lysine side chains ultimately generating the highly conserved α-(1,2)-glucosyl-β-(1,O)-galactosyl-5-hydroxylysine pattern. Malfunctions in the collagen lysine post-translational modification machinery is linked to multiple developmental pathologies as well as extracellular matrix alterations causing enhanced cellular proliferation and invasiveness of several solid tumors, prompting for an in-depth characterization of LH/PLOD and GLT25D/COLGALT enzyme families. Here, we present an integrative molecular study of GLT25D1/COLGALT, highlighting an elongated head-to-head homodimeric assembly characterized by an N-terminal segment of each monomer wrapping around its dimerization partner. Each monomer encompasses two Rossman fold-type domains (GT1 and GT2) separated by an extended linker. Both domains were found capable of binding Mn2+ cofactors and UDP-α-galactose donor substrates, resulting in four candidate catalytic sites per dimer. Site-directed mutagenesis and biochemical studies identify the C-terminal GT2 domain as the functional GLT25D1/COLGALT1 catalytic site, highlighting an unprecedented Glu-Asp-Asp motif critical for metal ion binding, and suggesting structural roles for the N-terminal GT1 essential for correct quaternary structure assembly. Conversely, dimerization was not a requirement for GLT25D1/COLGALT1 enzymatic activity in vitro , suggesting that the elongated enzyme homodimer assembly, resembling that of LH/PLOD binding partners, could represent a functional hallmark for correct recognition and successful processing of collagen lysine residues. ### Competing Interest Statement The authors have declared no competing interest.

20 June 2024- 2pm BST (9am NY / 10am Canada / 3pm CEST)- on Zoom Title: Greening your lab; Sustainable Practices & Benefits for your Life Science Lab Speakers: Julie Di Martino, New York Medical College, USA & Federico Forneris, University of Pavia, Italy