Juxta‐terminal Helix Unwinding as a Stabilizing Factor to Modulate the Dynamics of Transmembrane Helices. (10th February 2016)

• Record Type: Journal Article
• Authors: Mortazavi, Armin; Rajagopalan, Venkatesan; Sparks, Kelsey A.; Greathouse, Denise V.; Koeppe, Roger E.
• Is Part Of: Chembiochem. Volume 17:Number 6(2016)
• Page Start: 462
• Page End: 465
• Publication Date: 2016-02-10
• Subjects: GWALP23 -- protein–lipid interactions -- solid-state NMR spectroscopy -- transmembrane helix unwinding -- tryptophan; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201500656
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Transmembrane helices of integral membrane proteins often are flanked by interfacial aromatic residues that can serve as anchors to aid the stabilization of a tilted transmembrane orientation. Yet, physical factors that govern the orientation or dynamic averaging of individual transmembrane helices are not well understood and have not been adequately explained. Using solid‐state 2 H NMR spectroscopy to examine lipid bilayer‐incorporated model peptides of the GWALP23 (acetyl‐GGALW(LA)6 LWLAGA‐amide) family, we observed substantial unwinding at the terminals of several tilted helices spanning the membranes of DLPC, DMPC, or DOPC lipid bilayers. The fraying of helix ends might be vital for defining the dynamics and orientations of transmembrane helices in lipid bilayer membranes. Abstract : Unwinding underway : We synthesized and purified peptides to evaluate factors by solid‐state NMR that could stabilize a tilted orientation of transmembrane helices. Helix end fraying was identified as a critical feature for stabilizing the orientations and limiting the dynamics of transmembrane helices in membrane proteins.