Internal Triplication in the Structure of Human Ceruloplasmin

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1983 Jan 1

PMID 6571985

Citations 8

Authors

N Takahashi

R A BAUMAN

T L Ortel

F E Dwulet

C C Wang

F W Putnam

Affiliations

Soon will be listed here.

Abstract

Amino acid sequence analysis of the 67,000-dalton (67-kDal) fragment that is the amino-terminal half of human ceruloplasmin has revealed internal triplication in the primary structure of the entire molecule. This is illustrated by comparison of 620 residues representing homologous domains of the 67-kDal fragment and of the 50-kDal and 19-kDal fragments that together comprise the carboxyl-terminal half of the molecule. The polypeptide chain is divided into three covalently linked homologous segments, each of about 340 residues. All three homology units have about 30% identity in sequence, and each pair exhibits at least 40% identity. The statistical significance of the 3-fold internal duplication was established by computerized analysis of the sequence. These results and studies of the sites of limited proteolytic cleavage support a model for the ceruloplasmin molecule consisting of an alternating structure of six domains of two different kinds (or possibly nine domains of three kinds). The 3-fold internal homology suggests that the ceruloplasmin molecule evolved by tandem triplication of ancestral genes.

Citing Articles

Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites.

Bento I, Peixoto C, Zaitsev V, Lindley P Acta Crystallogr D Biol Crystallogr. 2007; 63(Pt 2):240-8.

PMID: 17242517 PMC: 2483498. DOI: 10.1107/S090744490604947X.

A third approach to gene prediction suggests thousands of additional human transcribed regions.

Glusman G, Qin S, El-Gewely M, Siegel A, Roach J, Hood L PLoS Comput Biol. 2006; 2(3):e18.

PMID: 16543943 PMC: 1391917. DOI: 10.1371/journal.pcbi.0020018.

Structural model of human ceruloplasmin based on internal triplication, hydrophilic/hydrophobic character, and secondary structure of domains.

Ortel T, Takahashi N, Putnam F Proc Natl Acad Sci U S A. 1984; 81(15):4761-5.

PMID: 6589622 PMC: 391570. DOI: 10.1073/pnas.81.15.4761.

Single-chain structure of human ceruloplasmin: the complete amino acid sequence of the whole molecule.

Takahashi N, Ortel T, Putnam F Proc Natl Acad Sci U S A. 1984; 81(2):390-4.

PMID: 6582496 PMC: 344682. DOI: 10.1073/pnas.81.2.390.

Coagulation factors V and VIII and ceruloplasmin constitute a family of structurally related proteins.

Church W, Jernigan R, Toole J, Hewick R, Knopf J, Knutson G Proc Natl Acad Sci U S A. 1984; 81(22):6934-7.

PMID: 6438625 PMC: 392050. DOI: 10.1073/pnas.81.22.6934.

References

Ryden L . Single-chain structure of human ceruloplasmin. Eur J Biochem. 1972; 26(3):380-6. DOI: 10.1111/j.1432-1033.1972.tb01777.x. View

Ryden L, Eaker D . The amino-acid sequences of three tryptic glycopeptides from human ceruloplasmin. Eur J Biochem. 1974; 44(1):171-80. DOI: 10.1111/j.1432-1033.1974.tb03470.x. View

Richardson J, Thomas K, Rubin B, Richardson D . Crystal structure of bovine Cu,Zn superoxide dismutase at 3 A resolution: chain tracing and metal ligands. Proc Natl Acad Sci U S A. 1975; 72(4):1349-53. PMC: 432531. DOI: 10.1073/pnas.72.4.1349. View

Kingston I, Kingston B, Putnam F . Chemical evidence that proteolytic cleavage causes the heterogeneity present in human ceruloplasmin preparations. Proc Natl Acad Sci U S A. 1977; 74(12):5377-81. PMC: 431726. DOI: 10.1073/pnas.74.12.5377. View

Adman E, Stenkamp R, Sieker L, Jensen L . A crystallographic model for azurin a 3 A resolution. J Mol Biol. 1978; 123(1):35-47. DOI: 10.1016/0022-2836(78)90375-3. View

Moshkov K, Lakatos S, Hajdu J, Zavodsky P, NEIFAKH S . Proteolysis of human ceruloplasmin. Some peptide bonds are particularly susceptible to proteolytic attack. Eur J Biochem. 1979; 94(1):127-34. DOI: 10.1111/j.1432-1033.1979.tb12879.x. View

Kingston I, Kingston B, Putnam F . Complete amino acid sequence of a histidine-rich proteolytic fragment of human ceruloplasmin. Proc Natl Acad Sci U S A. 1979; 76(4):1668-72. PMC: 383451. DOI: 10.1073/pnas.76.4.1668. View

Samsonidze T, Moshkov K, Kiselev N, NEIFAKH S . Electron microscope study on human ceruloplasmin. Int J Pept Protein Res. 1979; 14(2):161-8. DOI: 10.1111/j.1399-3011.1979.tb01739.x. View

Kingston I, Kingston B, Putnam F . Primary structure of a histidine-rich proteolytic fragment of human ceruloplasmin. II. Amino acid sequence of the tryptic peptides. J Biol Chem. 1980; 255(7):2886-96. View

10.

Noyer M, Dwulet F, Hao Y, Putnam F . Purification and characterization of undegraded human ceruloplasmin. Anal Biochem. 1980; 102(2):450-8. DOI: 10.1016/0003-2697(80)90181-5. View

11.

Pickart L, Freedman J, Loker W, Peisach J, Perkins C, Stenkamp R . Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature. 1980; 288(5792):715-7. DOI: 10.1038/288715a0. View

12.

Dwulet F, Putnam F . Complete amino acid sequence of a 50,000-dalton fragment of human ceruloplasmin. Proc Natl Acad Sci U S A. 1981; 78(2):790-4. PMC: 319888. DOI: 10.1073/pnas.78.2.790. View

13.

Dwulet F, Putnam F . Internal duplication and evolution of human ceruloplasmin. Proc Natl Acad Sci U S A. 1981; 78(5):2805-9. PMC: 319446. DOI: 10.1073/pnas.78.5.2805. View

14.

Doolittle R . Similar amino acid sequences: chance or common ancestry?. Science. 1981; 214(4517):149-59. DOI: 10.1126/science.7280687. View

15.

Ryden L, Norder H . Covalent chromatography as a means of isolating thiol peptides from large proteins: application to human ceruloplasmin. J Chromatogr. 1981; 215:341-50. DOI: 10.1016/s0021-9673(00)81413-2. View

16.

Prozorovski V, Rashkovetski L, Shavlovski M, Vasiliev V, NEIFAKH S . Evidence that human ceruloplasmin molecule consists of homologous parts. Int J Pept Protein Res. 1982; 19(1):40-53. DOI: 10.1111/j.1399-3011.1982.tb03021.x. View

17.

Tetaert D, Takahashi N, PUTMAN F . Purification of glycopeptides of human ceruloplasmin and immunoglobulin D by high-pressure liquid chromatography. Anal Biochem. 1982; 123(2):430-7. DOI: 10.1016/0003-2697(82)90468-7. View