C-mannosylation of human hyaluronidase 1: Possible roles for secretion and enzymatic activity

Yuki Goto, Yuki Niwa, Takehiro Suzuki, Naoshi Dohmae, Kazuo Umezawa, Siro Simizu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Protein glycosylation, one of the post-translational modifications, is important for many protein functions, such as protein stability, folding and secretion. In the protein glycosylation, C-mannosylation was first identified in ribonuclease 2, and some proteins have been reported to be C-mannosylated; however, effects of its modifications for target proteins remain unclear. Hyaluronidase 1 (HYAL1), degrading hyaluronic acid (HA), has two predicted C-mannosylation sites at Trp130 and Trp321. In this study, we examined whether HYAL1 is C-mannosylated or not, and the effect of C-mannosylation on HYAL1. Using mass spectrometry, we first demonstrated that intracellular HYAL1 is C-mannosylated at Trp130 but not at Trp 321. Surprisingly, although HYAL1 was secreted into conditioned medium and it possessed enzymatic activity, secreted HYAL1 was not C-mannosylated. Computer simulation demonstrated that C-mannosylation of HYAL1 at Trp130 changed conformation of the catalytic active site, and faced Glu131 in the opposite direction toward its substrate, HA, indicating that C-mannosylation will negatively regulate its secretion, and will attenuate its enzymatic activity. Taken together, this is the first report that demonstrates the presence of C-mannosylation among HYAL family proteins, and our results suggest possible roles of C-mannosylation for secretion and enzymatic activity.

Original languageEnglish
Pages (from-to)344-350
Number of pages7
JournalInternational journal of oncology
Volume45
Issue number1
DOIs
Publication statusPublished - 2014 Jul

Keywords

  • C-mannosylation
  • Glycosylation
  • Hyaluronidase
  • Mass spectrometry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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