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@ARTICLE{Banci:96611,
author = {Banci, L. and Bertini, I. and Boca, M. and Calderone, V.
and Cantini, F. and Girotto, S. and Vieru, M. and DESY},
title = {{S}tructural and dynamic aspects related to oligomerization
of apo {SOD}1 and its mutants.},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {106},
issn = {1091-6490},
address = {Washington, DC},
publisher = {Academy},
reportid = {PHPPUBDB-20353},
pages = {6980-6985},
year = {2009},
abstract = {The structural and dynamical properties of the metal-free
form of WT human superoxide dismutase 1 (SOD1) and its
familial amyotrophic lateral sclerosis (fALS)-related
mutants, T54R and I113T, were characterized both in
solution, through NMR, and in the crystal, through X-ray
diffraction. We found that all 3 X-ray structures show
significant structural disorder in 2 loop regions that are,
at variance, well defined in the fully-metalated structures.
Interestingly, the apo state crystallizes only at low
temperatures, whereas all 3 proteins in the metalated form
crystallize at any temperature, suggesting that
crystallization selects one of the most stable conformations
among the manifold adopted by the apo form in solution.
Indeed, NMR experiments show that the protein in solution is
highly disordered, sampling a large range of conformations.
The large conformational variability of the apo state allows
the free reduced cysteine Cys-6 to become highly solvent
accessible in solution, whereas it is essentially buried in
the metalated state and the crystal structures. Such solvent
accessibility, together with that of Cys-111, accounts for
the tendency to oligomerization of the metal-free state. The
present results suggest that the investigation of the
solution state coupled with that of the crystal state can
provide major insights into SOD1 pathway toward
oligomerization in relation to fALS.},
keywords = {Apoproteins: chemistry / Apoproteins: genetics /
Apoproteins: metabolism / Crystallography, X-Ray / Humans /
Models, Molecular / Mutation: genetics / Nuclear Magnetic
Resonance, Biomolecular / Protein Multimerization / Protein
Structure, Quaternary / Protein Structure, Secondary /
Protein Structure, Tertiary / Superoxide Dismutase:
chemistry / Superoxide Dismutase: genetics / Superoxide
Dismutase: metabolism / Apoproteins (NLM Chemicals) /
superoxide dismutase 1 (NLM Chemicals) / Superoxide
Dismutase (NLM Chemicals)},
cin = {EMBL},
ddc = {000},
cid = {$I:(DE-H253)EMBL_-2012_-20130307$},
pnm = {DORIS Beamline BW7 (POF1-550)},
pid = {G:(DE-H253)POF1-BW7-20130405},
experiment = {EXP:(DE-H253)D-BW7-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:19369197},
pmc = {pmc:PMC2678485},
UT = {WOS:000265584500022},
doi = {10.1073/pnas.0809845106},
url = {https://bib-pubdb1.desy.de/record/96611},
}