Under pressure that splits a family in two. The case of lipocalin family

PLoS One. 2012;7(11):e50489. doi: 10.1371/journal.pone.0050489. Epub 2012 Nov 27.

Abstract

The lipocalin family is typically composed of small proteins characterized by a range of different molecular recognition properties. Odorant binding proteins (OBPs) are a class of proteins of this family devoted to the transport of small hydrophobic molecules in the nasal mucosa of vertebrates. Among OBPs, bovine OBP (bOBP) is of great interest for its peculiar structural organization, characterized by a domain swapping of its two monomeric subunits. The effect of pressure on unfolding and refolding of native dimeric bOBP and of an engineered monomeric form has been investigated by theoretical and experimental studies under pressure. A coherent model explains the pressure-induced protein structural changes: i) the substrate-bound protein stays in its native configuration up to 330 MPa, where it loses its substrate; ii) the substrate-free protein dissociates into monomers at 200 MPa; and iii) the monomeric substrate-free form unfolds at 120 MPa. Molecular dynamics simulations showed that the pressure-induced tertiary structural changes that accompany the quaternary structural changes are mainly localized at the interface between the monomers. Interestingly, pressure-induced unfolding is reversible, but dimerization and substrate binding can no longer occur. The volume of the unfolding kinetic transition state of the monomer has been found to be similar to that of the folded state. This suggests that its refolding requires relatively large structural and/or hydrational changes, explaining thus the relatively low stability of the monomeric form of this class of proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Fluorescence
  • Lipocalins / chemistry*
  • Lipocalins / metabolism*
  • Models, Theoretical
  • Molecular Dynamics Simulation
  • Pressure*
  • Protein Conformation
  • Protein Folding
  • Protein Multimerization
  • Receptors, Odorant / chemistry
  • Receptors, Odorant / metabolism

Substances

  • Lipocalins
  • Receptors, Odorant
  • odorant-binding protein

Grants and funding

This work is in the frame of the CNR Commessa “Progettazione e Sviluppo di Innovative Metodologie Diagnostiche per la Sicurezza Alimentare e Salute Umana” (SD; MS; AV). This work was funded by EDA “Nanocap” project (A-1084-RT-GC) (SD, MS, AV). This work was also partially funded by FLAGSHIP “InterOmics” project (PB.P05), and FIRB project “ItalBioNet” (RBPR05ZK2Z and RBIN064YAT_003) (AM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.