ABO blood group A transferase and its codon 69 substitution enzymes synthesize FORS1 antigen of FORS blood group system
Yamamoto, Miyako (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Tarasco, Maria Cristiana (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Cid, Emili (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Kobayashi, Hidetomo (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Yamamoto, Fumiichiro (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Universitat Autònoma de Barcelona

Date:	2019
Abstract:	Human histo-blood group A transferase (AT) catalyzes the biosynthesis of oligosaccharide A antigen important in blood transfusion and cell/tissue/organ transplantation. This enzyme may synthesize Forssman antigen (FORS1) of the FORS blood group system when exon 3 or 4 of the AT mRNA is deleted and/or the LeuGlyGly tripeptide at codons 266-268 of AT is replaced by GlyGlyAla. The Met69Ser/Thr substitutions also confer weak Forssman glycolipid synthase (FS) activity. In this study, we prepared the human AT derivative constructs containing any of the 20 amino acids at codon 69 with and without the GlyGlyAla substitution, transfected DNA to newly generated COS1(B3GALNT1 + A4GALT) cells expressing an enhanced level of globoside (Gb4), the FS acceptor substrate, and immunologically examined the FORS1 expression. Our results showed that all those substitution constructs at codon 69 exhibited FS activity. The combination with GlyGlyAla significantly increased the activity. The conserved methionine residue in the ABO, but not GBGT1, gene-encoded proteins may implicate its contribution to the separation of these genes in genetic evolution. Surprisingly, with increased Gb4 availability, the original human AT with the methionine residue at codon 69 was also demonstrated to synthesize FORS1, providing another molecular mechanism of FORS1 appearance in cancer of ordinary FORS1-negative individuals.
Grants:	Instituto de Salud Carlos III PI11-00454 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR1269 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR529
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Glycobiology ; Immunochemistry ; Immunogenetics
Published in:	Scientific reports, Vol. 9 Núm. 1 (january 2019) , p. 9717, ISSN 2045-2322

DOI: 10.1038/s41598-019-46029-7
PMID: 31273262

11 p, 2.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles