This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Spontaneous peptide insertion and self-assembly to form functional pores or channels in membrane are involved in a wide range of biological functions. Despite the great fundamental and biomedical importance, the precise mechanisms of the actions of these peptides remain poorly understood at molecular level. This limitation is related to both (1) a lack of suitable molecular modeling tools for simulating such complex processes and (2) lack of simple model peptide systems to systematically investigate various factors under controlled conditions to uncover the underlying basic principles. The long-term goal of the proposed studies is to develop a multi-scale computational framework and simultaneously exploit novel model peptide systems to obtain a molecular-level understanding of the physical principles of insertion and self-assembly of membrane peptides.
The first aim i s to develop a flexible coarse-grained (CG) protein-lipid force field that are both efficient and realistic enough to provide an accurate description of conformational equilibria of helical peptides and its dependence on membrane binding and peptide-peptide associations.
The second aim i s to utilize direct CG simulations and free energy calculations to understand how peptide sequence, solution conditions and lipid properties determine the spontaneous insertion and assembly of peptides in biological membranes. Specific roles of folding or assembly in insertion will be examined using two established model systems including TMX-1/TMX-3 and the GpA dimer. The main focus is to exploit amphipathic peptides derived the second transmembrane helix of the glycine receptor (M2GlyR) as a paradigm for understanding how folding, insertion and assembly are linked altogether for actions of helical membrane peptides.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017686-08
Application #
7959802
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
2009-07-01
Project End
2010-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
8
Fiscal Year
2009
Total Cost
$72,978
Indirect Cost
Name
Kansas State University
Department
Anatomy/Cell Biology
Type
Schools of Veterinary Medicine
DUNS #
929773554
City
Manhattan
State
KS
Country
United States
Zip Code
66506
Ishiguro, Susumu; Kawabata, Atsushi; Zulbaran-Rojas, Alejandro et al. (2018) Co-treatment with a C1B5 peptide of protein kinase C? and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation. Biochem Biophys Res Commun 495:962-968
Kudo, Takayuki; Wangemann, Philine; Marcus, Daniel C (2018) Claudin expression during early postnatal development of the murine cochlea. BMC Physiol 18:1
Paper, Janet M; Mukherjee, Thiya; Schrick, Kathrin (2018) Bioorthogonal click chemistry for fluorescence imaging of choline phospholipids in plants. Plant Methods 14:31
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Liu, Qinfang; Miller, Laura C; Blecha, Frank et al. (2017) Reduction of infection by inhibiting mTOR pathway is associated with reversed repression of type I interferon by porcine reproductive and respiratory syndrome virus. J Gen Virol 98:1316-1328
Miyazaki, Hiromitsu; Wangemann, Philine; Marcus, Daniel C (2016) The gastric H,K-ATPase in stria vascularis contributes to pH regulation of cochlear endolymph but not to K secretion. BMC Physiol 17:1
Krishnamoorthy, Gayathri; Reimann, Katrin; Wangemann, Philine (2016) Ryanodine-induced vasoconstriction of the gerbil spiral modiolar artery depends on the Ca(2+) sensitivity but not on Ca(2+) sparks or BK channels. BMC Physiol 16:6
Montero-AstĂșa, Mauricio; Ullman, Diane E; Whitfield, Anna E (2016) Salivary gland morphology, tissue tropism and the progression of tospovirus infection in Frankliniella occidentalis. Virology 493:39-51
Dib, Lea H; Ortega, M Teresa; Melgarejo, Tonatiuh et al. (2016) Establishment and characterization of DB-1: a leptin receptor-deficient murine macrophage cell line. Cytotechnology 68:921-33
Ohta, Naomi; Ishiguro, Susumu; Kawabata, Atsushi et al. (2015) Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes. PLoS One 10:e0123756

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