Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3

Luigi Scietti, Antonella Chiapparino, Francesca De Giorgi, Marco Fumagalli, Lela Khoriauli, Solomon Nergadze, Shibom Basu, Vincent Olieric, Lucia Cucca, Blerida Banushi, Antonella Profumo, Elena Giulotto, Paul Gissen and Federico Forneris ()
Additional contact information
Luigi Scietti: University of Pavia
Antonella Chiapparino: University of Pavia
Francesca De Giorgi: University of Pavia
Marco Fumagalli: University of Pavia
Lela Khoriauli: University of Pavia
Solomon Nergadze: University of Pavia
Shibom Basu: Swiss Light Source, Paul Scherrer Institut
Vincent Olieric: Swiss Light Source, Paul Scherrer Institut
Lucia Cucca: University of Pavia
Blerida Banushi: University College London
Antonella Profumo: University of Pavia
Elena Giulotto: University of Pavia
Paul Gissen: University College London
Federico Forneris: University of Pavia

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Lysyl hydroxylases catalyze hydroxylation of collagen lysines, and sustain essential roles in extracellular matrix (ECM) maturation and remodeling. Malfunctions in these enzymes cause severe connective tissue disorders. Human lysyl hydroxylase 3 (LH3/PLOD3) bears multiple enzymatic activities, as it catalyzes collagen lysine hydroxylation and also their subsequent glycosylation. Our understanding of LH3 functions is currently hampered by lack of molecular structure information. Here, we present high resolution crystal structures of full-length human LH3 in complex with cofactors and donor substrates. The elongated homodimeric LH3 architecture shows two distinct catalytic sites at the N- and C-terminal boundaries of each monomer, separated by an accessory domain. The glycosyltransferase domain displays distinguishing features compared to other known glycosyltransferases. Known disease-related mutations map in close proximity to the catalytic sites. Collectively, our results provide a structural framework characterizing the multiple functions of LH3, and the molecular mechanisms of collagen-related diseases involving human lysyl hydroxylases.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-05631-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05631-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-05631-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().