Title :
Lysyl hydroxylase 3 modifies
lysine residues to facilitate oligomerization of mannan-binding
lectin
Abstract :
- Lysyl hydroxylase 3 3 (LH3 ) is a multifunctional protein with lysyl hydroxylase , galactosyltransferase and glucosyltransferase activities
- The LH3 has been shown to modify the lysine residues both in collagens and also in some collagenous proteins
- In this study we show for the first time that LH3 is essential for catalyzing formation of the glucosylgalactosylhydroxylysines of mannan-binding lectin ( MBL ), the first component of the lectin pathway of complement activation
- Furthermore, loss of the terminal glucose units on the derivatized lysine residues in mouse embryonic fibroblasts lacking the LH3 protein leads to defective disulphide bonding and oligomerization of rat MBL-A , with a decrease in the proportion of the larger functional MBL oligomers
- The oligomerization could be completely restored with the full length LH3 or the amino-terminal fragment of LH3 that possesses the glycosyltransferase activities
- Our results confirm that LH3 is the only enzyme capable of glucosylating the galactosylhydroxylysine residues in proteins with a collagenous domain
- In mice lacking the lysyl hydroxylase activity of LH3 , but with untouched galactosyltransferase and glucosyltransferase activities, reduced circulating MBL-A levels were observed
- Oligomerization was normal, however and residual lysyl hydroxylation was compensated in part by other lysyl hydroxylase isoenzymes
- Our data suggest that LH3 is commonly involved in biosynthesis of collagenous proteins and the glucosylation of galactosylhydroxylysines residues by LH3 is crucial for the formation of the functional high-molecular weight MBL oligomers