title: Curvature sensing MARCKS-ED peptides bind to membranes in a stereo-independent manner.
abstract: Membrane curvature and lipid composition plays a critical role in interchanging of matter and energy in cells. Peptide curvature sensors are known to activate signaling pathways and promote molecular transport across cell membranes. Recently, the 25-mer MARCKS-ED peptide, which is derived from the effector domain of the myristoylated alanine-rich C kinase substrate protein, has been reported to selectively recognize highly curved membrane surfaces. Our previous studies indicated that the naturally occurring L-MARCKS-ED peptide could simultaneously detect both phosphatidylserine and curvature. Here, we demonstrate that D-MARCKS-ED, composed by unnatural D-amino acids, has the same activities as its enantiomer, L-MARCKS-ED, as a curvature and lipid sensor. An atomistic molecular dynamics simulation suggests that D-MARCKS-ED may change from linear to a boat conformation upon binding to the membrane. Comparable enhancement of fluorescence intensity was observed between D- and L-MARCKS-ED peptides, indicating similar binding affinities. Meanwhile, circular dichroism spectra of D- and L-MARCKS-ED are almost symmetrical both in the presence and absence of liposomes. These results suggest similar behavior of artificial D- and natural L-MARCKS-ED peptides when binding to curved membranes. Our studies may contribute to further understanding of how MARCKS-ED senses membrane curvature as well as provide a new direction to develop novel membrane curvature probes.
authors: Center of Basic Molecular Science, Department of Chemistry, Tsinghua University, Beijing, China, 100082.
authors: Lei
authors: L
authors: Yan
authors: Department of Chemistry and Biochemistry, the BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80309-0596, USA.
authors: Armando Jerome
authors: AJ
authors: de Jesus
authors: Department of Chemistry and Biochemistry, the BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80309-0596, USA.
authors: Ryo
authors: R
authors: Tamura
authors: Department of Chemistry and Biochemistry, the BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80309-0596, USA.
authors: Victoria
authors: V
authors: Li
authors: Center of Basic Molecular Science, Department of Chemistry, Tsinghua University, Beijing, China, 100082.
authors: Kui
authors: K
authors: Cheng
authors: Center of Basic Molecular Science, Department of Chemistry, Tsinghua University, Beijing, China, 100082.|Department of Chemistry and Biochemistry, the BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80309-0596, USA.
authors: Hang
authors: H
authors: Yin
mesh_terms: D001572:Benzofurans / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010718:Phosphatidylserines / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D001572:Benzofurans; D005456:Fluorescent Dyes; D047908:Intracellular Signaling Peptides and Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D008565:Membrane Proteins; D010718:Phosphatidylserines; D000076250:Myristoylated Alanine-Rich C Kinase Substrate
keywords: MARCKS-ED; membrane curvature; simulation; unnatural peptides