English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Lysyl hydroxylase (LH) is a peripheral membrane protein in the lumen of the endoplasmic reticulum (ER) that catalyses hydroxylation of lysine residues in collagenous sequences. Previously, we have mapped its primary ER localization motif within a 40-amino acid segment at its C-terminus. Here, we have characterized this localization mechanism in more detail, and our results indicate that this segment confers ER residency in a KDEL-receptor-independent manner, and without any apparent recycling of the enzyme between the Golgi apparatus and the ER. In addition, we show that a rather long peptide region, rather than a specific peptide sequence per se, is required for efficient retention of a reporter protein in the ER. Accordingly, the minimal retention motif was found to require the last 32 C-terminal amino acids, and sequential substitution of all five charged residues within this critical segment interfered only marginally with the retention or association of the enzyme with the ER membranes. Moreover, our fold-recognition and structure-prediction analyses suggested that this critical peptide segment forms an extended loop within LH's iron-binding domain, and that this loop is exposed and readily accessible for binding. Collectively, our results define a novel retrieval-independent retention mechanism in the ER.

Retrieval-independent localization of lysyl hydroxylase in the endoplasmic reticulum via a peptide fold in its iron-binding domain