Alternative complement pathway activation fragment Ba binds to C3b. Evidence that formation of the factor B-C3b complex involves two discrete points of contact - PubMed (original) (raw)
. 1987 Feb 5;262(4):1519-25.
- PMID: 3643213
Free article
Alternative complement pathway activation fragment Ba binds to C3b. Evidence that formation of the factor B-C3b complex involves two discrete points of contact
E L Pryzdial et al. J Biol Chem. 1987.
Free article
Abstract
Alternative complement pathway C3 convertase formation involves the cleavage of C3b-associated factor B into fragments Ba and Bb. Whereas Bb, in complex with C3b, has proteolytic specificity toward native C3, the function of the Ba moiety in the formation and/or decay of alternative complement pathway C3 convertase is uncertain. Therefore, we have examined the effect of purified Ba fragment on both fluid-phase and surface-bound enzymatic activity and showed that whereas Ba could inhibit the rate of C3 convertase formation, the rate of intrinsic decay remained unaffected. A specific, metal ion-independent interaction between Ba and C3b was subsequently demonstrated by use of the cross-linking reagent dithiobis(succinimidyl propionate). When cell-associated 125I-B was activated by D, the dissociation of Bb fragment displayed simple first-order kinetics with a half-time of 2.4 min, this value being in reasonable agreement with the hemolytically determined decay rate of 1.8 min. In contrast, most of the Ba fragment undergoes rapid dissociation, but there is also evidence to suggest the establishment of a new equilibrium due to the ability of Ba to rebind to C3b. Cumulatively, these data are consistent with a model in which the attachment of intact B to C3b is mediated by two points of contact, one being in the Ba domain and the other in the Bb domain. Due to avidity effects, each of these interactions could be of relatively low intrinsic affinity, and the characteristic unidirectionality of alternative complement pathway C3 convertase decay may simply result from the low intrinsic association of "univalent" Bb for the C3b subunit.
Similar articles
- Analysis of the interaction between properdin and factor B, components of the alternative-pathway C3 convertase of complement.
Farries TC, Lachmann PJ, Harrison RA. Farries TC, et al. Biochem J. 1988 Aug 1;253(3):667-75. doi: 10.1042/bj2530667. Biochem J. 1988. PMID: 3140783 Free PMC article. - Residual hemolytic and proteolytic activity expressed by Bb after decay-dissociation of C3b,Bb.
Fishelson Z, Müller-Eberhard HJ. Fishelson Z, et al. J Immunol. 1984 Mar;132(3):1425-9. J Immunol. 1984. PMID: 6229580 - The C3 convertase of the alternative pathway of human complement. Enzymic properties of the bimolecular proteinase.
Pangburn MK, Müller-Eberhard HJ. Pangburn MK, et al. Biochem J. 1986 May 1;235(3):723-30. doi: 10.1042/bj2350723. Biochem J. 1986. PMID: 3638964 Free PMC article. - Ba and Bb fragments of factor B activation: fragment production, biological activities, neoepitope expression and quantitation in clinical samples.
Kolb WP, Morrow PR, Tamerius JD. Kolb WP, et al. Complement Inflamm. 1989;6(3):175-204. doi: 10.1159/000463093. Complement Inflamm. 1989. PMID: 2472921 Review. - Pathways of complement activation in membranoproliferative glomerulonephritis and allograft rejection.
Fearon DT, Daha MR, Strom TB, Weiler JM, Carpenter CB, Austen KF. Fearon DT, et al. Transplant Proc. 1977 Mar;9(1):729-39. Transplant Proc. 1977. PMID: 325806 Review.
Cited by
- Low-molecular weight inhibitors of the alternative complement pathway.
Schubart A, Flohr S, Junt T, Eder J. Schubart A, et al. Immunol Rev. 2023 Jan;313(1):339-357. doi: 10.1111/imr.13143. Epub 2022 Oct 11. Immunol Rev. 2023. PMID: 36217774 Free PMC article. Review. - Mini-Factor H Modulates Complement-Dependent IL-6 and IL-10 Release in an Immune Cell Culture (PBMC) Model: Potential Benefits Against Cytokine Storm.
Kozma GT, Mészáros T, Bakos T, Hennies M, Bencze D, Uzonyi B, Győrffy B, Cedrone E, Dobrovolskaia MA, Józsi M, Szebeni J. Kozma GT, et al. Front Immunol. 2021 Apr 28;12:642860. doi: 10.3389/fimmu.2021.642860. eCollection 2021. Front Immunol. 2021. PMID: 33995361 Free PMC article. - Inhibition of the Complement Alternative Pathway by Chemically Modified DNA Aptamers That Bind with Picomolar Affinity to Factor B.
Xu X, Zhang C, Denton DT, O'Connell D, Drolet DW, Geisbrecht BV. Xu X, et al. J Immunol. 2021 Feb 15;206(4):861-873. doi: 10.4049/jimmunol.2001260. Epub 2021 Jan 8. J Immunol. 2021. PMID: 33419768 Free PMC article. - Renal Damage in Recurrent Atypical Hemolytic Uremic Syndrome Associated with C3 p.Ile1157Thr Gene Mutation.
Okabe M, Kobayashi A, Marumoto H, Koike K, Yamamoto I, Kawamura T, Tsuboi N, Yokoo T. Okabe M, et al. Intern Med. 2021 Mar 15;60(6):917-922. doi: 10.2169/internalmedicine.5716-20. Epub 2020 Oct 21. Intern Med. 2021. PMID: 33087669 Free PMC article. - Identification of C3b-Binding Small-Molecule Complement Inhibitors Using Cheminformatics.
Garcia BL, Skaff DA, Chatterjee A, Hanning A, Walker JK, Wyckoff GJ, Geisbrecht BV. Garcia BL, et al. J Immunol. 2017 May 1;198(9):3705-3718. doi: 10.4049/jimmunol.1601932. Epub 2017 Mar 15. J Immunol. 2017. PMID: 28298523 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous