2D-NMR reveals different populations of exposed lysine residues in the apoB-100 protein of electronegative and electropositive fractions of LDL particles

Francisco J. Blanco, Sandra Villegas, Sònia Benítez, Cristina Bancells, Tammo Diercks, Jordi Ordóñez-Llanos, José L. Sánchez-Quesada

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Abstract

Several potentially atherogenic LDL subfractions present low affinity for the LDL receptor, which result in impaired plasma clearance. Electronegative LDL [LDL(-)] is one of these minor subfractions and the molecular basis for its reduced receptor affinity is not well understood. In the present study, high-resolution 2D-NMR spectroscopy has been employed to characterize the surface-exposed lysine residues of the apolipoprotein (apo)B-100 protein in both LDL(-) and LDL(+) subfractions. LDL(+) showed two populations of lysine residues, similar to those previously described in total LDL. "Normal" Lys have a pka of 10.4 whereas "active" Lys have a pk a of 8.8 and have been suggested to be involved in receptor binding. In contrast to LDL(+), the LDL(-) subfraction presented a third type of Lys, named as "intermediate" Lys, with a different microenvironment and higher basicity (pka 10.7). These intermediate Lys cannot be reliably identified by 1D-NMR. Because the abundance of normal Lys is similar in LDL(+) and LDL(-), the intermediate Lys in the apoB-100 molcule of LDL(-) should come from a group of active Lys in LDL(+) particles that have a less basic microenvironment in the LDL(-) particle. These differences between LDL(+) and LDL(-) are indicative of a distinct conformation of apoB-100 that could be related to loss of affinity of LDL(-) for the LDL receptor. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)1560-1565
JournalJournal of Lipid Research
Volume51
Issue number6
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Apolipoprotein B-100
  • Electronegative low density lipoprotein
  • Two-dimensional-nuclear magnetic resonance

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