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. 1986 Dec;83(24):9807–9811. doi: 10.1073/pnas.83.24.9807

Individual exons encode the integral membrane domains of human myelin proteolipid protein.

H J Diehl, M Schaich, R M Budzinski, W Stoffel
PMCID: PMC387231  PMID: 3467339

Abstract

The gene encoding human proteolipid protein (PLP) was isolated from a human genomic library by hybridization with labeled DNA of a PLP-specific cDNA clone. The entire PLP gene spans approximately 17 kilobases. Restriction and sequence analysis revealed seven exons and six introns. The entire nucleotide sequences of the exons and of the exon-intron transitions were determined, and the intron lengths were measured. Exon I includes only ATGG of the translated region, the N-terminal methionine codon and G of glycine, the first amino acid of mature PLP. Each hydrophobic trans- and cis-membrane domain of PLP together with its adjacent hydrophilic sequence correlates closely with one exon of the gene except for the C-terminal transmembrane helix that is encoded by two exons. The amino acid sequence of human PLP derived from the nucleic acid sequence is highly conserved. Human and rat PLP are completely homologous, whereas only four amino acid residues are exchanged in bovine PLP sequence derived from protein sequencing and a partial cDNA clone. Homology search on the nucleic acid level among human, bovine, and rat brain PLPs indicates an unusually high homology in the coding regions. Hybridization analysis with DNA of human-rodent hybrid clones revealed that the gene encoding PLP segregates with human X chromosome in the region q13-q22.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balazs I., Purrello M., Kurnit D. M., Grzeschik K. H., Siniscalco M. Isolation and characterization of human random cDNA clones homologous to DNA from the X chromosome. Somat Cell Mol Genet. 1984 Jul;10(4):385–397. doi: 10.1007/BF01535634. [DOI] [PubMed] [Google Scholar]
  2. Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  4. Camerino G., Grzeschik K. H., Jaye M., De La Salle H., Tolstoshev P., Lecocq J. P., Heilig R., Mandel J. L. Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus). Proc Natl Acad Sci U S A. 1984 Jan;81(2):498–502. doi: 10.1073/pnas.81.2.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
  6. Colman D. R., Kreibich G., Frey A. B., Sabatini D. D. Synthesis and incorporation of myelin polypeptides into CNS myelin. J Cell Biol. 1982 Nov;95(2 Pt 1):598–608. doi: 10.1083/jcb.95.2.598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dautigny A., Alliel P. M., d'Auriol L., Pham Dinh D., Nussbaum J. L., Galibert F., Jollès P. Molecular cloning and nucleotide sequence of a cDNA clone coding for rat brain myelin proteolipid. FEBS Lett. 1985 Aug 19;188(1):33–36. doi: 10.1016/0014-5793(85)80869-3. [DOI] [PubMed] [Google Scholar]
  8. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  9. Milner R. J., Lai C., Nave K. A., Lenoir D., Ogata J., Sutcliffe J. G. Nucleotide sequences of two mRNAs for rat brain myelin proteolipid protein. Cell. 1985 Oct;42(3):931–939. doi: 10.1016/0092-8674(85)90289-2. [DOI] [PubMed] [Google Scholar]
  10. Naismith A. L., Hoffman-Chudzik E., Tsui L. C., Riordan J. R. Study of the expression of myelin proteolipid protein (lipophilin) using a cloned complementary DNA. Nucleic Acids Res. 1985 Oct 25;13(20):7413–7425. doi: 10.1093/nar/13.20.7413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  12. Schaich M., Budzinski R. M., Stoffel W. Cloned proteolipid protein and myelin basic protein cDNA. Transcription of the two genes during myelination. Biol Chem Hoppe Seyler. 1986 Aug;367(8):825–834. doi: 10.1515/bchm3.1986.367.2.825. [DOI] [PubMed] [Google Scholar]
  13. Stoffel W., Hillen H., Giersiefen H. Structure and molecular arrangement of proteolipid protein of central nervous system myelin. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5012–5016. doi: 10.1073/pnas.81.16.5012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Stoffel W., Hillen H., Schröder W., Deutzmann R. Lipophilin (proteolipid apoprotein) of brain white matter. Purification and amino acid sequence studies of the four tryptophan fragments. Hoppe Seylers Z Physiol Chem. 1982 Nov;363(11):1397–1407. doi: 10.1515/bchm2.1982.363.2.1397. [DOI] [PubMed] [Google Scholar]
  15. Südhof T. C., Goldstein J. L., Brown M. S., Russell D. W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985 May 17;228(4701):815–822. doi: 10.1126/science.2988123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Willard H. F., Riordan J. R. Assignment of the gene for myelin proteolipid protein to the X chromosome: implications for X-linked myelin disorders. Science. 1985 Nov 22;230(4728):940–942. doi: 10.1126/science.3840606. [DOI] [PubMed] [Google Scholar]

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