http://www.cnr.it/ontology/cnr/individuo/prodotto/ID11344
The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the full-length protein (Articolo in rivista)
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- Label
- The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the full-length protein (Articolo in rivista) (literal)
- Anno
- 2002-01-01T00:00:00+01:00 (literal)
- Alternative label
Ilari A (1), Johnson KA (2), Nastopoulos V (3), Verzili D (1), Zamparelli C (2), Colotti G (1), Tsernoglou D (2), Chiancone E. (1,2) (2002)
The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the full-length protein
in Journal of Molecular Biology
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- Ilari A (1), Johnson KA (2), Nastopoulos V (3), Verzili D (1), Zamparelli C (2), Colotti G (1), Tsernoglou D (2), Chiancone E. (1,2) (literal)
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- The interdisciplinary level of the paper is noteworthy: although the
techniques used are only of physico-chemical character, the topic has
important pathological implications.
It is published in an authoritative peer-reviewed journal, Journal of
Molecular Biology (impact factor year 2002: 5.826), and has been cited 6
times since its publication.
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- Rivista
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- E. Chiancone, Direttore IBPM (literal)
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- The paper presents crystal structure of the calcium-binding domain of
sorcin, a penta-EF hand (PEF) two-domain protein that upon Ca2+ binding
translocates reversibly from cytosol to membranes, where it interacts with
different target proteins. In muscle cells, the sorcin participates in
excitation-contraction coupling through the interaction with the ryanodine
receptor (RyR), the Na+-Ca2+ exchanger (NCX) and the a1-subunit of L-type
Ca2+ channels.
The structure of the calcium-binding domain provides insight into the Ca2+-
induced conformational changes that lead to target protein recognition. In
the model, the N- and C-terminal domains interact with each other in the
Ca2+-free form and these interactions are weakened upon Ca2+ binding.
Further, in the calcium-free form the N-terminal domain covers a large
hydrophobic surface which includes the two tryptophan residues on the D
helix. Upon Ca2+ binding, this hydrophobic surface becomes accessible for
target protein recognition, since loosening of the interactions between
the two domains permits their reorientation. This mechanism may be
applicable to all PEF proteins.
The outcome of the paper provides an explanation in molecular terms for a
recently described form of familial hypertrophic cardiomyopathy that is
associated with a missense mutation at the end of the D-helix (F112L) of
the sorcin molecule.
(literal)
- Note
- ISI Web of Science (WOS) (literal)
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- 1. CNR (Istituto di Biologia e Patologia Molecolari)
2. Uni Sapienza (Dipartimento di Scienze Biochimiche A. Rossi Fanelli)
3. Uni Patrasso (Grecia, Dipartimento di Chimica) (literal)
- Titolo
- The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the full-length protein (literal)
- Abstract
- Sorcin is a 21.6 kDa calcium binding protein, expressed in a number of mammalian tissues that belongs to the small, recently identified penta-EF-hand (PEF) family. Like all members of this family, sorcin undergoes a Ca2+-dependent translocation from cytosol to membranes where it binds to target proteins. For sorcin, the targets differ in different tissues, indicating that it takes part in a number of Ca2+-regulated processes. The sorcin monomer is organized in two domains like in all PEF proteins: a flexible, hydrophobic, glycine-rich N-terminal region and a calcium binding
C-terminal domain. In vitro, the PEF proteins are dimeric in their Ca2+-free form, but have a marked tendency to precipitate when bound to calcium. Stabilization of the dimeric structure is achieved by pairing of the uneven EF-hand, EF5. Sorcin can also form tetramers at acid pH. The
sorcin calcium binding domain (SCBD, residues 33-198) expressed in Escherichia coli was crystallized in the Ca2+-free form. The structure was solved by molecular replacement and was refined to 2.2 A with a crystallographic R-factor of 22.4 %. Interestingly, the asymmetric unit
contains two dimers. The structure of the SCBD leads to a model that explains the solution properties and describes the Ca2+-induced conformational changes. Phosphorylation studies show that the N-terminal domain hinders phosphorylation of SCBD, i.e. the rate of phosphorylation
increased twofold in the absence of the N-terminal region. In addition, previous fluorescence studies indicated that hydrophobic residues are exposed to solvent upon Ca2+ binding to full-length sorcin. The model accounts for these data by proposing that Ca2+ binding weakens the interactions between the two domains and leads to their reorientation, which exposes hydrophobic regions facilitating the Ca2+-dependent binding to target proteins at or near membranes. (literal)
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