Unusual Ultrastructure of Complement-component-C4b-binding Protein of Human Complement by Synchrotron X-ray Scattering and Hydrodynamic Analysis

Overview

Journal Biochem J

Specialty Biochemistry

Date 1986 Feb 1

PMID 3707527

Citations 19

Authors

S J Perkins

L P Chung

K B Reid

Affiliations

Soon will be listed here.

Abstract

Solution X-ray-scattering experiments with the use of synchrotron radiation on the human complement-component-C4b-binding protein showed that its RG is 13 nm and that its Mr is 550,000. From the known primary amino acid sequence and estimated carbohydrate content, C4b-binding protein is inferred to have a total of 7.4 +/- 1 subunits. Heptameric computer models for C4b-binding protein were based on the X-ray-scattering curve to a resolution of 6.4 nm, and literature values for sedimentation coefficients and electron-microscopy images. The macromolecule was represented by a bundle of seven arms held together at the C-terminal end and spaced out by a base containing 23% of C4b-binding protein by volume. If the overall length of each arm is assumed to be 33 nm as seen in electron microscopy, the solution data indicate an average arm-axis angle of 5-10 degrees. The seven arms of C4b-binding protein are found to be close together, in distinction to the splayed-out images seen in electron micrographs.

Citing Articles

Higher-order structure and proteoforms of co-occurring C4b-binding protein assemblies in human serum.

Kadava T, Hevler J, Kalaidopoulou Nteak S, Yin V, Strasser J, Preiner J EMBO J. 2024; 43(14):3009-3026.

PMID: 38811852 PMC: 11251186. DOI: 10.1038/s44318-024-00128-y.

Two-Step Size-Exclusion Nanofiltration of Prothrombin Complex Concentrate Using Nanocellulose-Based Filter Paper.

Manukyan L, Mantas A, Razumikhin M, Katalevsky A, Golubev E, Mihranyan A Biomedicines. 2020; 8(4).

PMID: 32224972 PMC: 7235758. DOI: 10.3390/biomedicines8040069.

Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein.

Buffalo C, Bahn-Suh A, Hirakis S, Biswas T, Amaro R, Nizet V Nat Microbiol. 2016; 1(11):16155.

PMID: 27595425 PMC: 5014329. DOI: 10.1038/nmicrobiol.2016.155.

TFPI cofactor function of protein S: essential role of the protein S SHBG-like domain.

Reglinska-Matveyev N, Andersson H, Rezende S, Dahlback B, Crawley J, Lane D Blood. 2014; 123(25):3979-87.

PMID: 24740810 PMC: 4064334. DOI: 10.1182/blood-2014-01-551812.

Recombinant mouse sperm ZP3-binding protein (ZP3R/sp56) forms a high order oligomer that binds eggs and inhibits mouse fertilization in vitro.

Buffone M, Zhuang T, Ord T, Hui L, Moss S, Gerton G J Biol Chem. 2008; 283(18):12438-45.

PMID: 18316377 PMC: 2431013. DOI: 10.1074/jbc.M706421200.

References

Dunn J, Spiro R . The alpha 2-macroglobulin of human plasma. I. Isolation and composition. J Biol Chem. 1967; 242(23):5549-55. View

KRATKY O . X-RAY SMALL ANGLE SCATTERING WITH SUBSTANCES OF BIOLOGICAL INTEREST IN DILUTED SOLUTIONS. Prog Biophys Mol Biol. 1963; 13:105-73. DOI: 10.1016/s0079-6107(63)80015-2. View

Schmid K, Kaufmann H, Isemura S, Bauer F, Emura J, Motoyama T . Structure of 1 -acid glycoprotein. The complete amino acid sequence, multiple amino acid substitutions, and homology with the immunoglobulins. Biochemistry. 1973; 12(14):2711-24. DOI: 10.1021/bi00738a026. View

Reid K, Lowe D, Porter R . Isolation and characterization of C1q, a subcomponent of the first component of complement, from human and rabbit sera. Biochem J. 1972; 130(3):749-63. PMC: 1174513. DOI: 10.1042/bj1300749. View

Chothia C . Structural invariants in protein folding. Nature. 1975; 254(5498):304-8. DOI: 10.1038/254304a0. View

Tack B, Prahl J . Third component of human complement: purification from plasma and physicochemical characterization. Biochemistry. 1976; 15(20):4513-21. DOI: 10.1021/bi00665a028. View

de la Torre J, Bloomfield V . Hydrodynamics of macromolecular complexes. III. Bacterial viruses. Biopolymers. 1977; 16(8):1779-93. DOI: 10.1002/bip.1977.360160813. View

Nagasawa S, Stroud R . Cleavage of C2 by C1s into the antigenically distinct fragments C2a and C2b: demonstration of binding of C2b to C4b. Proc Natl Acad Sci U S A. 1977; 74(7):2998-3001. PMC: 431380. DOI: 10.1073/pnas.74.7.2998. View

Curman B, Peterson P . Chemical characterization of human factor B of the alternate pathway of complement activation. Biochemistry. 1977; 16(24):5368-75. DOI: 10.1021/bi00643a031. View

10.

Scharfstein J, Ferreira A, Gigli I, NUSSENZWEIG V . Human C4-binding protein. I. Isolation and characterization. J Exp Med. 1978; 148(1):207-22. PMC: 2184907. DOI: 10.1084/jem.148.1.207. View

11.

Hall P, Roberts R . Physical and chemical properties of human plasma alpha2-macroglobulin. Biochem J. 1978; 173(1):27-38. PMC: 1185745. DOI: 10.1042/bj1730027. View

12.

Damaschun G, MULLER J, BIELKA H . Scattering studies of ribosomes and ribosomal components. Methods Enzymol. 1979; 59:706-50. DOI: 10.1016/0076-6879(79)59122-8. View

13.

Pilz I, Glatter O, KRATKY O . Small-angle X-ray scattering. Methods Enzymol. 1979; 61:148-249. DOI: 10.1016/0076-6879(79)61013-3. View

14.

Reid K . Complete amino acid sequences of the three collagen-like regions present in subcomponent C1q of the first component of human complement. Biochem J. 1979; 179(2):367-71. PMC: 1186634. DOI: 10.1042/bj1790367. View

15.

Reboul A, Thielens N, Villiers M, Colomb M . Structural changes in C4 produced by cleavage with C1-s. FEBS Lett. 1980; 115(1):118-22. DOI: 10.1016/0014-5793(80)80739-3. View

16.

Nagasawa S, Stroud R . Purification and characterization of a macromolecular weight cofactor for C3b-inactivator, C4bC3bINA-cofactor, of human plasma. Mol Immunol. 1980; 17(11):1365-72. DOI: 10.1016/0161-5890(80)90005-x. View

17.

Yoshima H, Matsumoto A, Mizuochi T, Kawasaki T, Kobata A . Comparative study of the carbohydrate moieties of rat and human plasma alpha 1-acid glycoproteins. J Biol Chem. 1981; 256(16):8476-84. View

18.

Reid K, Porter R . The proteolytic activation systems of complement. Annu Rev Biochem. 1981; 50:433-64. DOI: 10.1146/annurev.bi.50.070181.002245. View

19.

Villiers M, Reboul A, Thielens N, Colomb M . Purification and characterization of C4-binding protein from human serum. FEBS Lett. 1981; 132(1):49-54. DOI: 10.1016/0014-5793(81)80425-5. View

20.

Perkins S, Miller A, Hardingham T, Muir H . Physical properties of the hyaluronate binding region of proteoglycan from pig laryngeal cartilage. Densitometric and small-angle neutron scattering studies of carbohydrates and carbohydrate-protein macromolecules. J Mol Biol. 1981; 150(1):69-95. DOI: 10.1016/0022-2836(81)90325-9. View