Towards membrane protein design: PH-sensitive topology of histidine-containing polypeptides

被引:179
作者
Bechinger, B [1 ]
机构
[1] MAX PLANCK INST MOL PHYSIOL, D-44139 DORTMUND, GERMANY
关键词
phospholipid bilayer; solid-state NMR spectroscopy; pK values of histidine; alpha-helix orientation; protein-lipid interactions;
D O I
10.1006/jmbi.1996.0614
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hydrophobic and amphipathic alpha-helices act as independent functional units in immunogenic or fusogenic polypeptides and constitute important structural building blocks in larger membrane proteins. In order to quantitatively assess the interactions that determine the alignment of membrane-associated alpha-helices, hydrophobic model peptides containing histidine residues at selected sites were prepared by solid-phase peptide synthesis. CD and solution NMR spectroscopy show that these peptides assume alpha-helical secondary structures in micellar environments. The chemical shift alterations of the histidine side-chain protons during pH titration experiments indicate that the pK values of the histidine imidazole protons range from 4.9 to 6.6 in the presence of dodecylphosphocholine micelles. N-15 solid-state NMR spectroscopy was used to determine the membrane alignment of these peptide alpha-helices in uniaxially oriented phospholipid bilayers. The observed pH-dependent change of orientation of one of these model peptides is quantitatively described by a dynamic equilibrium governed by both electrostatic and hydrophobic protein-lipid interactions. The thermodynamic equations presented provide a means for the prediction of membrane protein structure and topology, as well as the future design of peptide channels and pharmaceuticals. (C) 1996 Academic Press Limited
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页码:768 / 775
页数:8
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