First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.


From Proteopedia

Jump to: navigation, search
3hs0, resolution 3.00Å ()
Ligands: ,
Gene: CFB, BF, BFD (Homo sapiens)
Activity: Alternative-complement-pathway C3/C5 convertase, with EC number
Related: 3hrz
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Cobra Venom Factor (CVF) in complex with human factor B

Publication Abstract from PubMed

Immune protection by the complement system critically depends on assembly of C3 convertases on the surface of pathogens and altered host cells. These short-lived protease complexes are formed through pro-convertases, which for the alternative pathway consist of the complement component C3b and the pro-enzyme factor B (FB). Here, we present the crystal structure at 2.2-A resolution, small-angle X-ray scattering and electron microscopy (EM) data of the pro-convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. FB is loaded onto CVF through its pro-peptide Ba segment by specific contacts, which explain the specificity for the homologous C3b over the native C3 and inactive products iC3b and C3c. The protease segment Bb binds the carboxy terminus of CVF through the metal-ion dependent adhesion site of the Von Willebrand factor A-type domain. A possible dynamic equilibrium between a 'loading' and 'activation' state of the pro-convertase may explain the observed difference between the crystal structure of CVFB and the EM structure of C3bB. These insights into formation of convertases provide a basis for further development of complement therapeutics.

Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex., Janssen BJ, Gomes L, Koning RI, Svergun DI, Koster AJ, Fritzinger DC, Vogel CW, Gros P, EMBO J. 2009 Aug 19;28(16):2469-78. Epub 2009 Jul 2. PMID:19574954

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.


[CFAB_HUMAN] Defects in CFB are a cause of susceptibility to hemolytic uremic syndrome atypical type 4 (AHUS4) [MIM:612924]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.[1][2]


[CFAB_HUMAN] Factor B which is part of the alternate pathway of the complement system is cleaved by factor D into 2 fragments: Ba and Bb. Bb, a serine protease, then combines with complement factor 3b to generate the C3 or C5 convertase. It has also been implicated in proliferation and differentiation of preactivated B-lymphocytes, rapid spreading of peripheral blood monocytes, stimulation of lymphocyte blastogenesis and lysis of erythrocytes. Ba inhibits the proliferation of preactivated B-lymphocytes. [CO3_NAJKA] Complement-activating protein in cobra venom. It is a structural and functional analog of complement component C3b, the activated form of C3. It binds factor B (CFB), which is subsequently cleaved by factor D (CFD) to form the bimolecular complex CVF/Bb. CVF/Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. Structurally, it resembles the C3b degradation product C3c, which is not able to form a C3/C5 convertase. Unlike C3b/Bb, CVF/Bb is a stable complex and completely resistant to the actions of complement regulatory factors H (CFH) and I (CFI). Therefore, CVF continuously activates complement resulting in the depletion of complement activity.

About this Structure

3hs0 is a 8 chain structure with sequence from Homo sapiens and Naja kaouthia. Full crystallographic information is available from OCA.

See Also


  • Janssen BJ, Gomes L, Koning RI, Svergun DI, Koster AJ, Fritzinger DC, Vogel CW, Gros P. Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex. EMBO J. 2009 Aug 19;28(16):2469-78. Epub 2009 Jul 2. PMID:19574954 doi:10.1038/emboj.2009.184
  1. Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Arranz EA, Garrido CA, Lopez-Trascasa M, Sanchez-Corral P, Morgan BP, Rodriguez de Cordoba S. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):240-5. Epub 2006 Dec 20. PMID:17182750 doi:10.1073/pnas.0603420103
  2. Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ. Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. Hum Mutat. 2010 Jun;31(6):E1445-60. doi: 10.1002/humu.21256. PMID:20513133 doi:10.1002/humu.21256

Proteopedia Page Contributors and Editors (what is this?)


Personal tools