Evidence for erythrocyte membrane glycoproteins being carriers of blood‐group P<sub>1</sub> determinants

Haselberger, C.; Schenkel‐Brunner, Helmut

doi:10.1016/0014-5793(82)81086-7

Cited by 17 publications

(4 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One view that remained largely unchallenged for over 20 years was that the human Gb3/CD77 synthase (α1,4-galactosyltransferase, P1/P k synthase; EC 2.4.1.228) could only use GSLs as acceptors to produce Gal-α1→4Gal-terminated glycans (Gb3 and P1). The presence of P1 glycotope on human glycoproteins was first suggested by (36) and tested by (37), who reported that P1-antiserum recognized band 4.5 (GLUT1) and, to a lesser extent, other erythrocyte membrane proteins. However, a subsequent study contradicted those results by showing a complete depletion of P1 determinants from erythrocyte membrane glycoproteins upon treatment with n-butanol (38).…”

Section: Discussionmentioning

confidence: 94%

Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry

Szymczak-Kulus

Weidler

Bereznicka

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

The human Gb3/CD77 synthase, encoded by the A4GALT gene, is an unusually promiscuous glycosyltransferase. It synthesizes the Galα1→4Gal linkage on two different glycosphingolipids (GSLs), producing globotriaosylceramide (Gb3, CD77, P k ) and the P1 antigen. Gb3 is the major receptor for Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli . A single amino acid substitution (p.Q211E) ramps up the enzyme’s promiscuity, rendering it able to attach Gal both to another Gal residue and to GalNAc, giving rise to NOR1 and NOR2 GSLs. Human Gb3/CD77 synthase was long believed to transfer Gal only to GSL acceptors, therefore its GSL products were, by default, considered the only human Stx receptors. Here, using soluble, recombinant human Gb3/CD77 synthase and p.Q211E mutein, we demonstrate that both enzymes can synthesize the P1 glycotope (terminal Galα1→4Galβ1→4GlcNAc-R) on a complex type N-glycan and a synthetic N-glycoprotein (saposin D). Moreover, by transfection of CHO-Lec2 cells with vectors encoding human Gb3/CD77 synthase and its p.Q211E mutein, we demonstrate that both enzymes produce P1 glycotopes on N-glycoproteins, with the mutein exhibiting elevated activity. These P1-terminated N-glycoproteins are recognized by Stx1 but not Stx2 B subunits. Finally, cytotoxicity assays show that Stx1 can use P1 N-glycoproteins produced in CHO-Lec2 cells as functional receptors. We conclude that Stx1 can recognize and use P1 N-glycoproteins in addition to its canonical GSL receptors to enter and kill the cells, while Stx2 can use GSLs only. Collectively, these results may have important implications for our understanding of the Shiga toxin pathology.

show abstract

Section: Discussionmentioning

confidence: 94%

Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry

Szymczak-Kulus

Weidler

Bereznicka

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Studies supporting both ideas have been published. 6,7 In a recent study from our laboratory, the ability of P1P k synthase to use acceptors on both types of carriers was supported by the detection of P1 on human RBC glycoproteins. We also showed a dosage-dependent effect of A4GALT genotype on the level of P1 staining of RBC membrane proteins and, in addition, reported data supporting the idea that P1 appeared to be mainly carried on N-glycans in glycoproteins.…”

Section: Biochemistrymentioning

confidence: 92%

The P1PK blood group system: revisited and resolved

Stenfelt

Hellberg²,

Westman

et al. 2020

Immunohematology

View full text Add to dashboard Cite

This update on the P1PK blood group system (Hellberg Å, Westman JS, Thuresson B, Olsson ML. P1PK: the blood group system that changed its name and expanded. Immunohematology 2013;29:25–33) provides recent findings concerning the P1PK blood group system that have both challenged and confirmed old theories. The glycosphingolipids can no longer be considered the sole carriers of the antigens in this system because the P1 antigen has been detected on human red blood cell glycoproteins. New indications suggest that P1Pk synthase activity truly depends on the DXD motif, and the genetic background and molecular mechanism behind the common P1 and P2 phenotypes were found to depend on transcriptional regulation. Transcription factors bind the P1 allele selectively to a motif around rs5751348 in a regulatory region of A4GALT, which enhances transcription of the gene. Nonetheless, unexplained differences in antigen expression between individuals remain.

show abstract

“…It has been debated whether the P k and P1 antigens exist on glycoproteins present in the human RBC membrane or if glycolipids are the only membrane components carrying these epitopes [47,48]. However, a recent publication showed evidence that the P1 antigen can be detected on human RBC glycoproteins [49].…”

Section: Biochemistrymentioning

confidence: 99%

P1PK: a blood group system with an identity crisis

Hellberg¹

2019

ISBT Science Series

View full text Add to dashboard Cite

The P1PK blood group system (ISBT no. 003) was previously called the P blood group system, and the number of included antigens has varied over time. The history of the system is complicated and sometimes confusing, since several changes to the nomenclature have been made. Furthermore, the association between the antigens and their genetic home has raised many questions, as well as the long-standing enigma regarding the molecular mechanism underlying the common P 1 and P 2 phenotypes. Step by step, the biochemical and genetic basis underlying the antigens expressed in this system has been revealed. This review will start with the historical background and continue with the latest findings, answering some of the questions such as why individuals with p phenotype lack not only P k and P expression, but also P1, and whether the P1 antigens exist on both glycolipids and glycoproteins on the human red blood cells.

show abstract

Evidence for erythrocyte membrane glycoproteins being carriers of blood‐group P₁ determinants

Cited by 17 publications

References 12 publications

Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry

Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry

The P1PK blood group system: revisited and resolved

P1PK: a blood group system with an identity crisis

Contact Info

Product

Resources

About

Evidence for erythrocyte membrane glycoproteins being carriers of blood‐group P1 determinants

Cited by 17 publications

References 12 publications

Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry

Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry

The P1PK blood group system: revisited and resolved

P1PK: a blood group system with an identity crisis

Contact Info

Product

Resources

About

Evidence for erythrocyte membrane glycoproteins being carriers of blood‐group P₁ determinants