Carbohydrates located on the top of the "cap" contribute to the adhesive and enzymatic functions of vascular adhesion protein-1

Sanna-Mari Maula, Tiina Salminen, Sam Kaitaniemi, Yvonne Nymalm, David J. Smith, Sirpa Jalkanen

Research output: Contribution to journalArticleScientificpeer-review

23 Citations (Scopus)

Abstract

Vascular adhesion protein 1 (VAP-1) is an endothelial adhesion molecule with an enzymatic activity. It deaminates biogenic amines, resulting in the formation of aldehydes and hydrogen peroxide. During the enzymatic reaction a transient Schiff base is formed between endothelial VAP-1 and its leukocytic ligand, and this interaction is important for lymphocyte adhesion. VAP-1 monomer has six potential N-linked, and three putative O-linked glycosylation sites and an SSSS sequence potentially forming an attachment site for an adjacent O-linked site. In this work we modeled the carbohydrate decorations on a structural model of VAP-1, and studied which of those potential glycosylation sites are utilized, and whether those decorations accessible to a lymphocyte ligand are important in lymphocyte adhesion and enzymatic activity of VAP-1. We show that, unlike the O-linked attachment sites, all six N-linked glycosylation sites are in use. Furthermore, mutation of the N-linked attachment sites strategically located on the top of the molecule reduces lymphocyte adhesion in non-static conditions, and enhances the catalytic activity of membrane-bound human VAP-1 in static conditions, suggesting that glycosylation regulates the functional properties of VAP-1.

Original languageEnglish
Pages (from-to)2718-2727
Number of pages10
JournalEuropean Journal of Immunology
Volume35
Issue number9
DOIs
Publication statusPublished - Sept 2005
MoE publication typeA1 Journal article-refereed

Keywords

  • Amine Oxidase (Copper-Containing)/chemistry
  • Animals
  • CHO Cells
  • Cell Adhesion/immunology
  • Cell Adhesion Molecules/chemistry
  • Cricetinae
  • Endothelial Cells/cytology
  • Flow Cytometry
  • Glycosylation
  • Immunoblotting
  • Isoelectric Focusing
  • Lymphocytes/cytology
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Rats
  • Thoracic Surgery, Video-Assisted
  • Transfection

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