Orientation and dynamics of synthetic transbilayer polypeptides containing GpATM dimerization motifs.

Abstract:

:Deuterium NMR spectroscopy was used to study how the positioning of a dimerization motif within a transbilayer polypeptide influences its orientation and dynamics in bilayers. Three polypeptide variants comprising glycophorin A transmembrane (GpATM) dimerization motifs incorporated into lysine-terminated poly-leucine-alanine helices were mixed into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine multilamellar vesicles. The variants differed in orientation of the motif segment around the helix axis with respect to the peptide ends. Polypeptides were labeled with methyl-deuterated alanines at positions that were identically situated relative to the peptide ends (Ala-20 and Ala-22) and at two positions within the motif. An analysis of quadrupole splittings revealed similar tilts and orientations of the peptide ends for all three variants, suggesting that average orientations were dominated by interactions at the bilayer surface. For one variant, however, fast orientational fluctuations about the helix axis were significantly smaller. This may indicate some perturbation of peptide dynamics and conformation by interactions that are sensitive to the motif orientation relative to the peptide ends. For the variant that displayed distinct dynamics, one orientation consistent with observed splittings corresponded to the motif being situated such that its two glycines were particularly accessible to adjacent peptides.

journal_name

Biophys J

journal_title

Biophysical journal

authors

McDonald MC,Booth V,Morrow MR

doi

10.1016/j.bpj.2010.12.3725

subject

Has Abstract

pub_date

2011-02-02 00:00:00

pages

656-664

issue

3

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(11)00002-6

journal_volume

100

pub_type

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