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PDBsum entry 4upg
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Metal binding protein
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PDB id
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4upg
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References listed in PDB file
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Key reference
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Title
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Structural basis of sorcin-Mediated calcium-Dependent signal transduction.
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Authors
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A.Ilari,
A.Fiorillo,
E.Poser,
V.S.Lalioti,
G.N.Sundell,
Y.Ivarsson,
I.Genovese,
G.Colotti.
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Ref.
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Sci Rep, 2015,
5,
16828.
[DOI no: ]
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PubMed id
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Abstract
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Sorcin is an essential penta-EF hand calcium binding protein, able to confer the
multi-drug resistance phenotype to drug-sensitive cancer cells and to reduce
Endoplasmic Reticulum stress and cell death. Sorcin silencing blocks cell cycle
progression in mitosis and induces cell death by triggering apoptosis. Sorcin
participates in the modulation of calcium homeostasis and in calcium-dependent
cell signalling in normal and cancer cells. The molecular basis of Sorcin action
is yet unknown. The X-ray structures of Sorcin in the apo (apoSor) and in
calcium bound form (CaSor) reveal the structural basis of Sorcin action: calcium
binding to the EF1-3 hands promotes a large conformational change, involving a
movement of the long D-helix joining the EF1-EF2 sub-domain to EF3 and the
opening of EF1. This movement promotes the exposure of a hydrophobic pocket,
which can accommodate in CaSor the portion of its N-terminal domain displaying
the consensus binding motif identified by phage display experiments. This domain
inhibits the interaction of sorcin with PDCD6, a protein that carries the Sorcin
consensus motif, co-localizes with Sorcin in the perinuclear region of the cell
and in the midbody and is involved in the onset of apoptosis.
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