Human complement C3b/C4b receptor (CRI) mRNA polymorphism that correlates with the CRI allelic molecular weight polymorphism

V. M. Holers, D. D. Chaplin, J. F. Leykam, B. A. Gruner, V. Kumar, J. P. Atkinson

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Abstract

The human C3b/C4b receptor (CR1) is a M(r) ~ 200,000 single-chain integral membrane glycoprotein of human erythrocytes and leukocytes. It functions both as a receptor for C3b- and C4b-coated ligands and as a regulator of complement activation. Prior structural studies have defined an unusual molecular weight allelic polymorphism in which the allelic products differ in molecular weight by as much as 90,000. On peripheral blood cells there is codominant expression of CR1 gene products of M(r) 190,000 (A), 220,000 (B), 160,000 (C), and 250,000 (D). Results of prior biosynthetic and tryptic peptide mapping experiments have suggested that the most likely basis for the allelic molecular weight differences is at the polypeptide level. In order to define further the molecular basis for these molecular weight differences, human CR1 was purified to homogeneity, tryptic peptide fragments were isolated by HPLC and sequenced, oligonucleotide probes were prepared, and a CR1 cDNA was identified. A subclone of this CR1 cDNA was used as a probe of RNA blots of Epstein-Barr virus-transformed cell lines expressing the allelic variants. Each allelic variant encodes two distinct transcripts. A mRNA size polymorphism was identified that correlated with the gene product molecular weight polymorphism. This finding, in addition to a prior report of several homologous repeats in CR1, is consistent with the hypothesis that the molecular weight polymorphism is determined at the genomic level and may have been generated by unequal crossing-over.

Original languageEnglish
Pages (from-to)2459-2463
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number8
DOIs
StatePublished - 1987

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