Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Nov;84(21):7403–7407. doi: 10.1073/pnas.84.21.7403

Structural changes and metal binding by proalbumins and other amino-terminal genetic variants of human serum albumin.

N Takahashi 1, Y Takahashi 1, F W Putnam 1
PMCID: PMC299304  PMID: 3478700

Abstract

Proalbumins are rare genetic variants of human serum albumin containing a basic propeptide that is not removed during post-transcriptional processing because of a mutation in the site of excision, an Arg-Arg sequence. We have identified the amino acid substitutions in three different types of proalbumins designated Gainesville, Taipei, and Takefu. The first two proalbumins are identical to previously described proalbumins of the Christchurch and Lille types, respectively, and exhibit the characteristic properties of susceptibility to tryptic cleavage and of lower metal-binding affinity. Takefu is a third type of proalbumin and resists tryptic cleavage because of the substitution Arg-1----Pro. Each of the first two types of proalbumins has been identified in geographically separate, ethnically diverse populations and therefore must have arisen by independent mutations. There is some tendency for mutations in albumin to cluster in the propeptide sequence. Although the substitution His3----Gln in the genetic variant albumin Nagasaki-3 decreases metal-binding affinity, mutations further down the polypeptide chain have no such effect, nor is there any reduction of copper-binding affinity in albumin from patients with Wilson disease.

Full text

PDF
7405

Images in this article

7404Image
on p.7404

Selected References

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

  1. Abdo Y., Rousseaux J., Dautrevaux M. Proalbumin Lille, a new variant of human serum albumin. FEBS Lett. 1981 Aug 31;131(2):286–288. doi: 10.1016/0014-5793(81)80386-9. [DOI] [PubMed] [Google Scholar]
  2. Bathurst I. C., Brennan S. O., Carrell R. W., Cousens L. S., Brake A. J., Barr P. J. Yeast KEX2 protease has the properties of a human proalbumin converting enzyme. Science. 1987 Jan 16;235(4786):348–350. doi: 10.1126/science.3541206. [DOI] [PubMed] [Google Scholar]
  3. Brennan S. O., Carrell R. W. A circulating variant of human proalbumin. Nature. 1978 Aug 31;274(5674):908–909. doi: 10.1038/274908a0. [DOI] [PubMed] [Google Scholar]
  4. Brennan S. O., Carrell R. W. Functional abnormality of proalbumin Christchurch. Biochim Biophys Acta. 1980 Jan 24;621(1):83–88. doi: 10.1016/0005-2795(80)90064-1. [DOI] [PubMed] [Google Scholar]
  5. Brennan S. O. The molecular abnormality of albumin Parklands: 365 Asp----His. Biochim Biophys Acta. 1985 Aug 23;830(3):320–324. doi: 10.1016/0167-4838(85)90289-4. [DOI] [PubMed] [Google Scholar]
  6. Fine J. M., Abdo Y., Rochu D., Rousseaux J., Dautrevaux M. Identification of the human albumin variant "Gainesville" with proalbumin "Christchurch". Rev Fr Transfus Immunohematol. 1983 Sep;26(4):341–346. doi: 10.1016/s0338-4535(83)80078-6. [DOI] [PubMed] [Google Scholar]
  7. Fine J. M., Marneux M., Rochu D. Human albumin genetic variants: an attempt at a classification of European allotypes. Am J Hum Genet. 1987 Mar;40(3):278–286. [PMC free article] [PubMed] [Google Scholar]
  8. Frydman M., Bonné-Tamir B., Farrer L. A., Conneally P. M., Magazanik A., Ashbel S., Goldwitch Z. Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase D locus. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1819–1821. doi: 10.1073/pnas.82.6.1819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Galliano M., Minchiotti L., Ferri G., Iadarola P., Zapponi M. C., Fine J. M. Structural characterization of the human albumin variant "Pollibauer". Rev Fr Transfus Immunohematol. 1984 Oct;27(5):597–602. doi: 10.1016/s0338-4535(84)80080-x. [DOI] [PubMed] [Google Scholar]
  10. Galliano M., Minchiotti L., Iadarola P., Stoppini M., Ferri G., Castellani A. A. The molecular defect of albumin Tagliacozzo: 313 Lys----Asn. FEBS Lett. 1986 Nov 24;208(2):364–368. doi: 10.1016/0014-5793(86)81050-x. [DOI] [PubMed] [Google Scholar]
  11. Galliano M., Minchiotti L., Iadarola P., Zapponi M. C., Ferri G., Castellani A. A. Structural characterization of a chain termination mutant of human serum albumin. J Biol Chem. 1986 Mar 25;261(9):4283–4287. [PubMed] [Google Scholar]
  12. Iadarola P., Minchiotti L., Galliano M. Localization of the amino acid substitution site in a fast migrating variant of human serum albumin. FEBS Lett. 1985 Jan 21;180(1):85–88. doi: 10.1016/0014-5793(85)80237-4. [DOI] [PubMed] [Google Scholar]
  13. Judah J. D., Quinn P. S. Calcium ion-dependent vesicle fusion in the conversion of proalbumin to albumin. Nature. 1978 Jan 26;271(5643):384–385. doi: 10.1038/271384a0. [DOI] [PubMed] [Google Scholar]
  14. Lau T., Sunderman F. W., Jr, Agarwal S. S., Sutnick A. I., Blumberg B. S. Genetics of albumin Gainesville, a new variant of human serum albumin. Nature. 1969 Jan 4;221(5175):66–68. doi: 10.1038/221066a0. [DOI] [PubMed] [Google Scholar]
  15. Matsuda Y., Ogushi F., Ogawa K., Katunuma N. Structure and properties of albumin Tokushima and its proteolytic processing by cathepsin B in vitro. J Biochem. 1986 Aug;100(2):375–379. doi: 10.1093/oxfordjournals.jbchem.a121724. [DOI] [PubMed] [Google Scholar]
  16. Minghetti P. P., Ruffner D. E., Kuang W. J., Dennison O. E., Hawkins J. W., Beattie W. G., Dugaiczyk A. Molecular structure of the human albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4. J Biol Chem. 1986 May 25;261(15):6747–6757. [PubMed] [Google Scholar]
  17. Peters T., Jr Serum albumin. Adv Protein Chem. 1985;37:161–245. doi: 10.1016/s0065-3233(08)60065-0. [DOI] [PubMed] [Google Scholar]
  18. Takahashi N., Takahashi Y., Blumberg B. S., Putnam F. W. Amino acid substitutions in genetic variants of human serum albumin and in sequences inferred from molecular cloning. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4413–4417. doi: 10.1073/pnas.84.13.4413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Takahashi N., Takahashi Y., Ishioka N., Blumberg B. S., Putnam F. W. Application of an automated tandem high-performance liquid chromatographic system to peptide mapping of genetic variants of human serum albumin. J Chromatogr. 1986 May 30;359:181–191. doi: 10.1016/0021-9673(86)80072-3. [DOI] [PubMed] [Google Scholar]
  20. Weitkamp L. R., McDermid E. M., Neel J. V., Fine J. M., Petrini C., Bonazzi L., Ortali V., Porta F., Tanis R., Harris D. J. Additional data on the population distribution of human serum albumin genes; three new variants. Ann Hum Genet. 1973 Oct;37(2):219–226. doi: 10.1111/j.1469-1809.1973.tb01829.x. [DOI] [PubMed] [Google Scholar]
  21. Winter W. P., Weitkamp L. R., Rucknagel D. L. Amino acid substitution in two identical inherited human serum albumin variants: albumin Oliphant and albumin Ann Arbor. Biochemistry. 1972 Feb 29;11(5):889–896. doi: 10.1021/bi00755a031. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES