Research and Development

@article{deJesus2016,

title = {Determinants of Curvature-Sensing Behavior for MARCKS-Fragment Peptides},

author = {Armando J. de Jesus and Ormacinda R. White and Aaron D. Flynn and Hang Yin},

url = {https://www.cell.com/biophysj/fulltext/S0006-3495(16)30168-0},

doi = {10.1016/j.bpj.2016.04.007},

year  = {2016},

date = {2016-05-10},

journal = {Biophysical Journal},

volume = {110},

number = {9},

pages = {1980-1992},

abstract = {It is increasingly recognized that membrane curvature plays an important role in various cellular activities such as signaling and trafficking, as well as key issues involving health and disease development. Thus, curvature-sensing peptides are essential to the study and detection of highly curved bilayer structures. The effector domain of myristoylated alanine-rich C-kinase substrate (MARCKS-ED) has been demonstrated to have curvature-sensing ability. Research of the MARCKS-ED has further revealed that its Lys and Phe residues play an essential role in how MARCKS-ED detects and binds to curved bilayers. MARCKS-ED has the added property of being a lower-molecular-weight curvature sensor, which offers advantages in production. With that in mind, this work investigates peptide-sequence-related factors that influence curvature sensing and explores whether peptide fragments of even shorter length can function as curvature sensors. Using both experimental and computational methods, we studied the curvature-sensing capabilities of seven fragments of MARCKS-ED. Two of the longer fragments were designed from approximately the two halves of the full-length peptide whereas the five shorter fragments were taken from the central stretch of MARCKS-ED. Fully atomistic molecular dynamics simulations show that the fragments that remain bound to the bilayer exhibit interactions with the bilayer similar to that of the full-length MARCKS-ED peptide. Fluorescence enhancement and anisotropy assays, meanwhile, reveal that five of the MARCKS fragments possess the ability to sense membrane curvature. Based on the sequences of the curvature-sensing fragments, it appears that the ability to sense curvature involves a balance between the numbers of positively charged residues and hydrophobic anchoring residues. Together, these findings help crystallize our understanding of the molecular mechanisms underpinning the curvature-sensing behaviors of peptides, which will prove useful in the design of future curvature sensors.},

keywords = {-},

pubstate = {published},

tppubtype = {article}

}

@article{deJesus2013,

title = {Changes in lipid density induce membrane curvature},

author = {Armando J. de Jesus and Noah Kastelowitz and Hang Yin},

url = {https://pubs.rsc.org/en/content/articlelanding/2013/RA/c3ra42332h},

doi = {10.1039/C3RA42332H},

year  = {2013},

date = {2013-06-18},

journal = {RSC Advances},

volume = {3},

number = {33},

pages = {13622-13625},

abstract = {Highly curved bilayer lipid membranes make up the shell of many intra- and extracellular compartments, including organelles and vesicles. Using all-atom molecular dynamics simulations, we show that increasing the density of lipids in the bilayer membrane can induce the membrane to form a curved shape.},

keywords = {-},

pubstate = {published},

tppubtype = {article}

}