Faculty Collaboration Database

Apelin conformational and binding equilibria upon micelle interaction primarily depend on membrane-mimetic headgroup. Sci Rep 2017 Nov 13;7(1):15433

Date

11/15/2017

Pubmed ID

29133807

Pubmed Central ID

PMC5684411

DOI

10.1038/s41598-017-14784-0

Scopus ID

2-s2.0-85034078489 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

Apelin is one of two peptide hormones that activate the apelin receptor (AR or APJ) to regulate the cardiovascular system, central nervous system, and adipoinsular axis. Here, we apply circular dichroism (CD) spectropolarimetry and nuclear magnetic resonance (NMR) spectroscopy to characterize the potential membrane binding by the two longest bioactive apelin isoforms, apelin-55 and -36, using membrane-mimetic dodecylphosphocholine (DPC), sodium dodecyl sulfate (SDS), and 1-palmitoyl-2-hydroxy-sn-glycero-3-[phospho-rac-(1-glycerol)] (LPPG) micelles. Pulsed field gradient diffusion NMR experiments demonstrated preferential interaction of both apelin-55 and -36 with anionic SDS and LPPG micelles over zwitterionic DPC micelles. Chemical shift perturbations and changes in ps-ns scale dynamics of apelin-55 in all micelles were similarly localized along the polypeptide backbone, demonstrating clear dependence upon detergent headgroup, while comparison of chemical shifts between apelin-55 and apelin-36 showed negligible differences indicative of highly similar modes of micelle interaction. Notably, the observed behaviour was consistent with an ensemble averaged pair of free and bound states in fast exchange on the NMR timescale proportional to the fraction of micelle-bound protein, implying a similar conformational equilibrium regardless of headgroup and tailgroup. Membrane catalysis of apelin-AR binding would thus give rise to analogous behaviour in the essential C-terminal region common to all apelin isoforms.

Author List

Shin K, Sarker M, Huang SK, Rainey JK

Author

Kyungsoo Shin PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Apelin
Cell Membrane
Circular Dichroism
Detergents
Membranes, Artificial
Micelles
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Protein Isoforms
Protein Structure, Secondary
Recombinant Proteins