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Structure Analysis and Conformational Transitions of the Cell Penetrating Peptide Transportan 10 in the Membrane-Bound State

Fanghänel, Susanne; Wadhwani, Parvesh; Strandberg, Erik; Verdurmen, Wouter P. R.; Bürck, Jochen; Ehni, Sebastian; Mykhailiuk, Pavel K.; Afonin, Sergii; Gerthsen, Dagmar; Komarov, Igor V.; Brock, Roland; Ulrich, Anne S.

Structure analysis of the cell-penetrating peptide transportan 10 (TP10) revealed an exemplary range of different conformations in the membrane-bound state. The bipartite peptide (derived N-terminally from galanin and C-terminally from mastoparan) was found to exhibit prominent characteristics of (i) amphiphilic α-helices, (ii) intrinsically disordered peptides, as well as (iii) β-pleated amyloid fibrils, and these conformational states become interconverted as a function of concentration. We used a complementary approach of solid-state 19F-NMR and circular dichroism in oriented membrane samples to characterize the structural and dynamical behaviour of TP10 in its monomeric and aggregated forms. Nine different positions in the peptide were selectively substituted with either the L- or D-enantiomer of 3-(trifluoromethyl)-bicyclopent-[1.1.1]-1-ylglycine (CF3-Bpg) as a reporter group for 19F-NMR. Using the L-epimeric analogs, a comprehensive three-dimensional structure analysis was carried out in lipid bilayers at low peptide concentration, where TP10 is monomeric. While the N-terminal region is flexible and intrinsically unstructured within the plane of the lipid bilayer, the C-terminal α-helix is embedded in the membrane with an oblique tilt angle of ∼55° and in accordance with its amphiphilic profile. ... mehr

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DOI: 10.5445/IR/1000042220
DOI: 10.1371/journal.pone.0099653
Zitationen: 38
Web of Science
Zitationen: 32
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Baugestaltung (Inst. f. Baugest.)
Laboratorium für Elektronenmikroskopie (LEM)
Institut für Biologische Grenzflächen (IBG)
Center for Functional Nanostructures (CFN)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2014
Sprache Englisch
Identifikator ISSN: 1932-6203
KITopen-ID: 1000042220
HGF-Programm 47.02.02 (POF II, LK 01)
Synth. biomimetische Werkzeuge IBG 2
Erschienen in PLoS one
Band 9
Heft 6
Seiten Art.Nr. e99653
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Nachgewiesen in Scopus
Web of Science
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