Assessing the stabilization of P-glycoprotein's nucleotide-binding domains by the linker, using molecular dynamics

Ricardo J. Ferreira, Maria José U. Ferreira, Daniel J.V.A. Dos Santos

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

This paper focuses on the importance of the intermediate linker sequence for the stabilization of the cytoplasmic portion of murine P-glycoprotein, an ABC transporter involved in Multidrug Resistance (MDR) in cancer. Three putative protein-protein interaction areas were predicted to exist, two of them next to the C-terminal nucleotide-binding domain (NBD2) and the third one next to the inner leaflet interface of the lipid bilayer. These contact spots were confirmed by detailed contact maps from structures obtained before and after a 100 ns molecular dynamics production run, allowing a more thorough characterization of the type and number of residues involved in protein-protein contacts. It was found that these contact surfaces are located next to several highly conserved motifs of ABC transporters, serving as anchor points and assisting the linker's 'damper' function.

Original languageEnglish
Pages (from-to)529-540
Number of pages12
JournalMolecular Informatics
Volume32
Issue number5-6
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

Keywords

  • Molecular dynamics
  • Nucleotide-binding sites
  • P-Glycoprotein
  • Protein-protein contacts

Fingerprint

Dive into the research topics of 'Assessing the stabilization of P-glycoprotein's nucleotide-binding domains by the linker, using molecular dynamics'. Together they form a unique fingerprint.

Cite this