Lysyl Hydroxylase 3 Modifies Lysine Residues to Facilitate Oligomerization of Mannan-Binding Lectin

De Montfort University Open Research Archive

Show simple item record

dc.contributor.author Risteli, M. en
dc.contributor.author Ruotsalainen, H. en
dc.contributor.author Bergmann, U. en
dc.contributor.author Venkatraman Girija, U. en
dc.contributor.author Wallis, R. en
dc.contributor.author Myllyla, R. en
dc.date.accessioned 2015-05-29T08:46:14Z
dc.date.available 2015-05-29T08:46:14Z
dc.date.issued 2014-11
dc.identifier.citation Risteli, M., Ruotsalainen, H., Bergmann, U., Venkatraman Girija, U., Wallis, R. and Myllyla, R. (2014) Lysyl Hydroxylase 3 Modifies Lysine Residues to Facilitate Oligomerization of Mannan-Binding Lectin. PLoS ONE, 9 (11), e113498 en
dc.identifier.other PMC4242627
dc.identifier.uri http://hdl.handle.net/2086/10991
dc.description.abstract Lysyl hydroxylase 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. en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.subject Lysyl Hydroxylase 3 en
dc.subject Mannan Binding Lectin en
dc.title Lysyl Hydroxylase 3 Modifies Lysine Residues to Facilitate Oligomerization of Mannan-Binding Lectin en
dc.type Article en
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0113498
dc.researchgroup Infectious Disease Research Group
dc.peerreviewed Yes en
dc.funder na en
dc.projectid na en


Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record