EurekaMag
+ Translate
+ Most Popular
Advantages and disadvantages of bordeaux mixture and of lime-sulphur used on apples in the growing season
Observations on the Umaria marine bed
10 years of hearing conservation in the Royal Air Force
Chocolate crumb - dairy ingredient for milk chocolate
Effect of daily gelatin ingestion on human scalp hair
Comparison of rice bran and maize bran as feeds for growing and fattening pigs
The composition of pampas-grass (Cortaderia argentea.)
The Accraian Series:
The mechanism of the Liebermann-Burchard reaction of sterols and triterpenes and their esters
Cerebrovascular Doppler ultrasound studies (cv-Doppler)
Toria: PT-303 - first national variety
Hair growth promoting activity of tridax procumbens
Productivity of Pekin x Khaki Campbell ducks
A stable cytosolic expression of VH antibody fragment directed against PVY NIa protein in transgenic potato plant confers partial protection against the virus
Solar treatment of wheat loose smut
Swimmers itch in the Lake of Garda
Bactofugation and the Bactotherm process
The effects of prefrontal lobotomy on aggressive behavior in dogs
Visual rating scales for screening whorl-stage corn for resistance to fall armyworm
Breakdown of seamounts at the trench axis, viewed from gravity anomaly
Kooken; pennsylvania's toughest cave
Recovery of new dinosaur and other fossils from the Early Cretaceous Arundel Clay facies (Potomac Group) of central Maryland, U.S.A
Zubor horny (Bison bonasus) v prirodnych podmienkach Slovensku
The extended Widal test in the diagnosis of fevers due to Salmonella infection
Hair of the american mastodon indicates an adaptation to a semi aquatic habitat

The role of the individual domains in the structure and function of the catalytic region of a modular serine protease, C1r


The role of the individual domains in the structure and function of the catalytic region of a modular serine protease, C1r



Journal of Immunology 167(9): 5202-5208



ISSN/ISBN: 0022-1767

PMID: 11673533

DOI: 10.4049/jimmunol.167.9.5202

The first enzymatic event in the classical pathway of complement activation is autoactivation of the C1r subcomponent of the C1 complex. Activated C1r then cleaves and activates zymogen C1s. C1r is a multidomain serine protease consisting of N-terminal alpha region interacting with other subcomponents and C-terminal gammaB region mediating proteolytic activity. The gammaB region consists of two complement control protein modules (CCP1, CCP2) and a serine protease domain (SP). To clarify the role of the individual domains in the structural and functional properties of the gammaB region we produced the CCP1-CCP2-SP (gammaB), the CCP2-SP, and the SP fragments in recombinant form in Escherichia coli. We successfully renatured the inclusion body proteins. After renaturation all three fragments were obtained in activated form and showed esterolytic activity on synthetic substrates similar to each other. To study the self-activation process in detail zymogen mutant forms of the three fragments were constructed and expressed. Our major statement is that the ability of autoactivation and C1s cleavage is an inherent property of the SP domain. We observed that the CCP2 module significantly increases proteolytic activity of the SP domain on natural substrate, C1s. Therefore, we propose that CCP2 module provides accessory binding sites. Differential scanning calorimetric measurements demonstrated that CCP2 domain greatly stabilizes the structure of SP domain. Deletion of CCP1 domain from the CCP1-CCP2-SP fragment results in the loss of the dimeric structure. Our experiments also provided evidence that dimerization of C1r is not a prerequisite for autoactivation.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 018178838

Download citation: RISBibTeXText

Related references

Structure of the human cytomegalovirus protease catalytic domain reveals a novel serine protease fold and catalytic triad. Cell 86(5): 835-843, 1996

Inhibition of Melanization by a Parasitoid Serine Protease Homolog Venom Protein Requires Both the Clip and the Non-Catalytic Protease-Like Domains. Insects 2(4): 509-514, 2011

Baculovirus-mediated expression of truncated modular fragments from the catalytic region of human complement serine protease C1s. Evidence for the involvement of both complement control protein modules in the recognition of the C4 protein substrate. Journal of Biological Chemistry 273(2): 1232-1239, 1998

Structure-function studies of the asparaginyl-tRNA synthetase from Fasciola gigantica: understanding the role of catalytic and non-catalytic domains. Biochemical Journal 475(21): 3377-3391, 2018

Molecular characterization of the catalytic domains of human complement serine protease C1r. Biochemistry 25(18): 5177-5182, 1986

Identification of three catalytic triad constituents and Asp-225 essential for function of lysine-specific serine protease, Achromobacter protease I. Journal of Biological Chemistry 269(25): 17025-17029, 1994

The 1.8 A structure of the complex between chymostatin and Streptomyces griseus protease A. A model for serine protease catalytic tetrahedral intermediates. Journal of Molecular Biology 183(1): 89-103, 1985

The 1.8 angstrom structure of the complex between chymostatin and streptomyces griseus protease a a model for serine protease catalytic tetrahedral intermediates. Journal of Molecular Biology 183(1): 89-104, 1985

Structure and catalytic regulatory function of ubiquitin specific protease 11 N-terminal and ubiquitin-like domains. Biochemistry 53(18): 2966-2978, 2014

Binding diversity of a noncovalent-type low-molecular-weight serine protease inhibitor and function of a catalytic water molecule: X-ray crystal structure of PKSI-527--inhibited trypsin. Journal of Biochemistry 129(3): 455-460, 2001

Structure of the catalytic fragment of mannan-binding lectin-associated serine protease 2. Molecular Immunology 40(2-4): 201, 2003

Crystal structure of a catalytic antibody with a serine protease active site. Science 265(5175): 1059-1064, 1994

Crystal structure of the catalytic domain of human complement c1s: a serine protease with a handle. Embo Journal 19(8): 1755-1765, 2000

Crystal structure of a novel viral protease with a serine/lysine catalytic dyad mechanism. Journal of Molecular Biology 358(5): 1378-1389, 2006

Catalytic role of a surface loop of the complement serine protease factor D. Journal of Immunology 154(11): 6073-6079, 1995