Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants (Articolo in rivista) (literal)

Anno

• 2003-01-01T00:00:00+01:00 (literal)

Alternative label

• Mella M, Colotti G, Zamparelli C, Verzili D , Ilari A , Chiancone E. (2003)
  Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants
  
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Mella M, Colotti G, Zamparelli C, Verzili D , Ilari A , Chiancone E. (literal)

Pagina inizio

• 24921 (literal)

Pagina fine

• 24928 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni

• The interdisciplinary level of the paper is high: it couples physico-chemical and biochemical data and has important implications for human pathology It is published in an authoritative peer-reviewed journal, The Journal of Biological Chemistry (impact factor year 2002: 7.258). (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 278 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto

• The experimental work presented in this paper is part of a study on the role of proteins belonging to the PEF (penta EF hand) family. PEF proteins, when calcium bound, translocate reversibly from cytosol to membrane(s) and thereby participate in calcium-mediated signal trasduction. The PEF protein under study, sorcin (SOluble Resistance related Calcium- binding proteIN) is involved in different calcium-triggered biochemical cascades since upon calcium binding it interacts with different target proteins, namely the ryanodine receptor (RyR), the Na+-Ca2+ exchanger (NCX) and the a1-subunit of L-type Ca2+ channels in muscle cells, presenilin 2 in human brain, annexin VII in adrenal medulla, differentiating myocytes and red blood cells. The paper proves the previously proposed mechanism of the calcium- dependent protein activation that entails a non canonical information transfer from EF3, the site with the highest affinity for calcium, to the rest of the molecule. The outcome of the article is of relevance given the recent assignment of an unusual form of familial hypertrophic cardiomyopathy to a sorcin missense mutation (F112L) in the EF3 site. (literal)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• 1. Uni Sapienza (Dipartimento di Scienze Biochimiche “A. Rossi Fanelli”) 2. CNR (Istituto di Biologia e Patologia Molecolari) (literal)

Titolo

• Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants (literal)

Abstract

• Sorcin is a typical penta-EF-hand protein that participates in Ca2+-regulated processes by translocating reversibly from cytosol to membranes, where it interacts with different target proteins in different tissues. Binding of two Ca2+/monomer triggers translocation, although EF1, EF2, and EF3 are potentially able to bind calcium at micromolar concentrations. To identify the functional pair, the conserved bidentate -Z glutamate in these EF-hands was mutated to yield E53Q-, E94A-, and E124A-sorcin, respectively. Limited structural perturbations occur only in E124A-sorcin due to involvement of Glu-124 in a network of interactions that comprise the long D helix connecting EF3 to EF2. The overall affinity for Ca2+ and for two sorcin targets, annexin VII and the ryanodine receptor, follows the order wild-type > E53Q- > E94A- > E124A-sorcin, indicating that disruption of EF3 has the largest functional impact and that disruption of EF2 and EF1 has progressively smaller effects. Based on this experimental evidence, EF3 and EF2, which are not paired in the canonical manner, are the functional EF-hands. Sorcin is proposed to be activated upon Ca2+ binding to EF3 and transmission of the conformational change at Glu-124 via the D helix to EF2 and from there to EF1 via the canonical structural/functional pairing. This mechanism may be applicable to all penta-EF-hand proteins. (literal)

Prodotto di

• Institute of molecular biology and pathology (IBPM) (Istituto)

Autore CNR

• GIANNI COLOTTI (Unità di personale interno)
• ANDREA ILARI (Unità di personale interno)
• EMILIA CHIANCONE (Unità di personale esterno)
• DANIELA VERZILI (Unità di personale interno)

Insieme di parole chiave

• Keywords of "Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants" (Insieme di parole chiave)

Incoming links:

Prodotto

• Institute of molecular biology and pathology (IBPM) (Istituto)

Autore CNR di

• EMILIA CHIANCONE (Unità di personale esterno)
• DANIELA VERZILI (Unità di personale interno)
• GIANNI COLOTTI (Unità di personale interno)
• ANDREA ILARI (Unità di personale interno)

Insieme di parole chiave di

• Keywords of "Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants" (Insieme di parole chiave)