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@ARTICLE{Chrabszczewska:461912,
author = {Chrabąszczewska, Magdalena and Sieradzan, Adam K. and
Rodziewicz-Motowidło, Sylwia and Grubb, Anders and Dobson,
Christopher M. and Kumita, Janet R. and Kozak, Maciej},
title = {{S}tructural {C}haracterization of {C}ovalently
{S}tabilized {H}uman {C}ystatin {C} {O}ligomers},
journal = {International journal of molecular sciences},
volume = {21},
number = {16},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {PUBDB-2021-03169},
pages = {5860},
year = {2020},
abstract = {Human cystatin C (HCC), a cysteine-protease inhibitor,
exists as a folded monomer under physiological conditions
but has the ability to self-assemble via domain swapping
into multimeric states, including oligomers with a
doughnut-like structure. The structure of the monomeric HCC
has been solved by X-ray crystallography, and a covalently
linked version of HCC (stab-1 HCC) is able to form stable
oligomeric species containing 10–12 monomeric subunits. We
have performed molecular modeling, and in conjunction with
experimental parameters obtained from atomic force
microscopy (AFM), transmission electron microscopy (TEM) and
small-angle X-ray scattering (SAXS) measurements, we observe
that the structures are essentially flat, with a height of
about 2 nm, and the distance between the outer edge of the
ring and the edge of the central cavity is ~5.1 nm. These
dimensions correspond to the height and diameter of one
stab-1 HCC subunit and we present a dodecamer model for
stabilized cystatin C oligomers using molecular dynamics
simulations and experimentally measured parameters. Given
that oligomeric species in protein aggregation reactions are
often transient and very highly heterogeneous, the
structural information presented here on these isolated
stab-1 HCC oligomers may be useful to further explore the
physiological relevance of different structural species of
cystatin C in relation to protein misfolding disease.},
cin = {EMBL-User / FS-PS},
ddc = {540},
cid = {I:(DE-H253)EMBL-User-20120814 / I:(DE-H253)FS-PS-20131107},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
experiment = {EXP:(DE-H253)D-D1.2-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {32824145},
UT = {WOS:000565053900001},
doi = {10.3390/ijms21165860},
url = {https://bib-pubdb1.desy.de/record/461912},
}