Simulative and experimental investigation on the cleavage site that generates the soluble human LOX-1

Silvia Biocca, Tania Arcangeli, Elisa Tagliaferri, Barbara Testa, Giulia Vindigni, Francesco Oteri, Alessandra Giorgi, Federico Iacovelli, Giuseppe Novelli, Alessandro Desideri, Mattia Falconi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger receptor that mediates the recognition, the binding and internalization of ox-LDL. A truncated soluble form of LOX-1 (sLOX-1) has been identified that, at elevated levels, has been associated to acute coronary syndrome. Human sLOX-1 is the extracellular part of membrane LOX-1 which is cleaved in the NECK domain with a mechanism that has not yet been identified. Purification of human sLOX-1 has been carried out to experimentally identify the cleavage site region within the NECK domain. Molecular modelling and classical molecular dynamics simulation techniques have been used to characterize the structural and dynamical properties of the LOX-1 NECK domain in the presence and absence of the CTLD recognition region, taking into account the obtained proteolysis results. The simulative data indicate that the NECK domain is stabilized by the coiled-coil heptad repeat motif along the simulations, shows a definite flexibility pattern and is characterized by specific electrostatic potentials. The detection of a mobile inter-helix space suggests an explanation for the in vivo susceptibility of the NECK domain to the proteolytic cleavage, validating the assumption that the NECK domain sequence is composed of a coiled-coil motif destabilized in specific regions of functional significance.

Original languageEnglish
Pages (from-to)9-18
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume540
Issue number1-2
DOIs
Publication statusPublished - 2013

Fingerprint

Class E Scavenger Receptors
Proteolysis
Scavenger Receptors
Molecular modeling
Purification
Molecular dynamics
Electrostatics
Membranes
Computer simulation
Molecular Dynamics Simulation
Acute Coronary Syndrome
Static Electricity
oxidized low density lipoprotein

Keywords

  • Classical molecular dynamics simulation
  • Coiled-coil structure
  • Molecular threading
  • NECK domain
  • Proteolytic cleavage
  • Soluble LOX-1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Biocca, S., Arcangeli, T., Tagliaferri, E., Testa, B., Vindigni, G., Oteri, F., ... Falconi, M. (2013). Simulative and experimental investigation on the cleavage site that generates the soluble human LOX-1. Archives of Biochemistry and Biophysics, 540(1-2), 9-18. https://doi.org/10.1016/j.abb.2013.10.001

Simulative and experimental investigation on the cleavage site that generates the soluble human LOX-1. / Biocca, Silvia; Arcangeli, Tania; Tagliaferri, Elisa; Testa, Barbara; Vindigni, Giulia; Oteri, Francesco; Giorgi, Alessandra; Iacovelli, Federico; Novelli, Giuseppe; Desideri, Alessandro; Falconi, Mattia.

In: Archives of Biochemistry and Biophysics, Vol. 540, No. 1-2, 2013, p. 9-18.

Research output: Contribution to journalArticle

Biocca, S, Arcangeli, T, Tagliaferri, E, Testa, B, Vindigni, G, Oteri, F, Giorgi, A, Iacovelli, F, Novelli, G, Desideri, A & Falconi, M 2013, 'Simulative and experimental investigation on the cleavage site that generates the soluble human LOX-1', Archives of Biochemistry and Biophysics, vol. 540, no. 1-2, pp. 9-18. https://doi.org/10.1016/j.abb.2013.10.001
Biocca, Silvia ; Arcangeli, Tania ; Tagliaferri, Elisa ; Testa, Barbara ; Vindigni, Giulia ; Oteri, Francesco ; Giorgi, Alessandra ; Iacovelli, Federico ; Novelli, Giuseppe ; Desideri, Alessandro ; Falconi, Mattia. / Simulative and experimental investigation on the cleavage site that generates the soluble human LOX-1. In: Archives of Biochemistry and Biophysics. 2013 ; Vol. 540, No. 1-2. pp. 9-18.
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