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@ARTICLE{Mortensen:328781,
author = {Mortensen, Sofia and Kidmose, Rune T. and Petersen, Steen
V. and Szilágyi, Ágnes and Prohászka, Zoltan and
Andersen, Gregers R.},
title = {{S}tructural {B}asis for the {F}unction of {C}omplement
{C}omponent {C}4 within the {C}lassical and {L}ectin
{P}athways of {C}omplement},
journal = {The journal of immunology},
volume = {194},
number = {11},
issn = {1550-6606},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {PUBDB-2017-05441},
pages = {5488 - 5496},
year = {2015},
abstract = {Complement component C4 is a central protein in the
classical and lectin pathways within the complement system.
During activation of complement, its major fragment C4b
becomes covalently attached to the surface of pathogens and
altered self-tissue, where it acts as an opsonin marking the
surface for removal. Moreover, C4b provides a platform for
assembly of the proteolytically active convertases that
mediate downstream complement activation by cleavage of C3
and C5. In this article, we present the crystal and solution
structures of the 195-kDa C4b. Our results provide the
molecular details of the rearrangement accompanying C4
cleavage and suggest intramolecular flexibility of C4b. The
conformations of C4b and its paralogue C3b are shown to be
remarkably conserved, suggesting that the convertases from
the classical and alternative pathways are likely to share
their overall architecture and mode of substrate
recognition. We propose an overall molecular model for the
classical pathway C5 convertase in complex with C5,
suggesting that C3b increases the affinity for the substrate
by inducing conformational changes in C4b rather than a
direct interaction with C5. C4b-specific features revealed
by our structural studies are probably involved in the
assembly of the classical pathway C3/C5 convertases and C4b
binding to regulators.},
cin = {EMBL-User},
ddc = {610},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {6G3 - PETRA III (POF3-622)},
pid = {G:(DE-HGF)POF3-6G3},
experiment = {EXP:(DE-H253)P-P12-20150101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000354905300049},
pubmed = {pmid:25911760},
doi = {10.4049/jimmunol.1500087},
url = {https://bib-pubdb1.desy.de/record/328781},
}