Lipids modulate the conformational dynamics of a secondary multidrug transporter

Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers

Study of the activation mechanisms of G protein-coupled receptors using molecular modeling

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Lipids Can Make Them Stick Together

To be active, membrane proteins often need to assemble into multimers either transiently or permanently. Using high-end mass spectrometry (MS), Robinson and colleagues show that the formation of transient multimers may require lipids at the interface while stable oligomers appear not to require such help.SCOPUS: sh.jinfo:eu-repo/semantics/publishe

Study of the activation mechanisms of G protein-coupled receptors using molecular modeling

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

LmrP from Lactoccoccus lactis: a tractable model to understand secondary multidrug transport in MFS

The secondary transporter LmrP from Lactoccoccus lactis is a remarkable model to study the molecular basis of secondary multidrug transport. This review article addresses more than twenty years of research about transport activity, substrates range, conformational dynamics and mechanistic models of drug export for LmrP. Several studies have shown that the transporter alternates between inward-open and outward-open conformations and that the transition is regulated by the protonation state of key acidic residues and is further modulated by the lipid environment.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prions

info:eu-repo/semantics/publishe

The diversity and possible functions of the inositol polyphosphate 5-phosphatases

Distinct forms of inositol and phosphatidylinositol polyphosphate 5-phosphatases selectively remove the phosphate from the 5-position of the inositol ring from both soluble and lipid substrates, i.e. inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), inositol 1,3,4, 5-tetrakisphosphate (Ins(1,3,4,5)P4), phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) or phosphatidylinositol 3,4, 5-trisphosphate (PtdIns(3,4,5)P3). In mammalian cells, this family contains a series of distinct genes and splice variants. All inositol polyphosphate 5-phosphatases share a 5-phosphatase domain and various protein modules probably responsible for specific cell localisation or recruitment (SH2 domain, proline-rich sequences, prenylation sites, etc.). Type I Ins(1,4,5)P3 5-phosphatase also uses Ins(1,3,4,5)P4 but not the phosphoinositides as substrates. This enzyme is targeted to specific membranes by means of a prenylation site. Type II 5-phosphatases can use both PtdIns(4,5)P2 and PtdIns(3,4,5)P3 as substrates. Five mammalian enzymes and multiple splice variants are known: INPP5P or inositol polyphosphate 5-phosphatase II, OCRL (a Golgi protein implicated in the Lowe oculocerebrorenal syndrome), synaptojanin (a protein involved in the recycling of synaptic vesicles), SHIP 1 and SHIP 2 (or SH2-containing inositol 5-phosphatases). As discussed in this review, the substrate specificity, regulatory mechanisms, subcellular localisation and tissue specificity indicate that the different 5-phosphatase isoforms may play specific roles. As known in the dephosphorylation of tyrosine containing substrates by the tyrosine protein phosphatases or in the metabolism of cyclic nucleotides by the cyclic nucleotide phosphodiesterases, inositol polyphosphate 5-phosphatases directly participate in the control of second messengers in response to both activation or inhibitory cell signalling.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

AlphaFold2 predicts the inward-facing conformation of the multidrug transporter LmrP

As part of the CASP competition, the protein structure prediction algorithm AlphaFold2 generated multiple models of the proton/drug antiporter LmrP. Previous distance restraints from double electron-electron resonance spectroscopy, a technique which reports distance distributions between spin labels attached to proteins, suggest that one of the lower-ranked models may have captured a conformation that has so far eluded experimental structure determination.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

3-D structure of g protein-coupled receptors

SCOPUS: ch.binfo:eu-repo/semantics/publishe