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Structural Characterization of the Chondroitin Sulfate motif binding to VAR2CSA in Placenta and Cancer
Author(s) -
Spliid Charlotte Bredo,
Toledo Alejandro Gomez,
Esko Jeffrey,
Clausen Thomas Mandel
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00445
Subject(s) - sulfation , placenta , chemistry , glycosaminoglycan , glucuronic acid , chondroitin sulfate , uronic acid , biochemistry , structural motif , biology , polysaccharide , genetics , pregnancy , fetus
Malaria parasites have evolved to express certain proteins called VAR2CSA on the surface of infected erythrocytes. This allows them to adhere to unique chondroitin sulfate (CS) motifs, which are only found in the placenta. It was recently discovered that VAR2CSA also binds to over 95% of all types of cancer. The exact structure of the CS chains, termed oncofetal CS (ofCS), has previously been reported to be mostly non‐sulfated with low levels of 4‐O‐sulfation in the placenta. In this study, we found that ofCS was ~90% 4‐O‐sulfated with the remaining ~10% being mostly 6‐O‐sulfated and 2‐O‐sulfated. Although previously thought to be purely glucuronic acid (GlcA) we found that ~25% of the uronic acid content consisted of iduronic acid (IdoA). Additionally, we identified that the CS quantity and chain length were significantly increased in placenta and colon tumors compared to healthy organs and colon. This increased CS availability along with the unique ofCS motif is likely what causes high specificity of VAR2CSA to placenta and cancer. Support or Funding Information VAR2 PharmaceuticalsGangstedfondenLouis‐Hansen Fonden