The three-dimensional structure of the 81-residue mercury transporter MerF determined in liquid crystalline phospholipid bilayers under physiological conditions by Rotationally Aligned (RA) solid-state NMR has two long helices, which extend well beyond the bilayer, with a well-defined interhelical loop. Truncation of the N-terminal 12 residues, which are mobile and unstructured when the protein is solubilized in micelles, results in a large structural rearrangement of the protein in bilayers. In the full-length protein, the N-terminal helix is aligned nearly parallel to the membrane normal and forms an extension of the first transmembrane helix. By contrast, this helix adopts a perpendicular orientation in the truncated protein. The close spatial proximity of the two Cys-containing metal binding sites in the three-dimensional structure of full-length MerF provides insights into possible transport mechanisms. These results demonstrate that major changes in protein structure can result from differences in amino acid sequence (e.g., full-length vs truncated proteins) as well as the use of a non-native membrane mimetic environment (e.g., micelles) vs liquid crystalline phospholipid bilayers. They provide further evidence of the importance of studying unmodified membrane proteins in near-native bilayer environments in order to obtain accurate structures that can be related to their functions.
%0 Journal Article
%1 lu_structure_2013
%A Lu, George J
%A Tian, Ye
%A Vora, Nemil
%A Marassi, Francesca M
%A Opella, Stanley J
%D 2013
%J J. Am. Chem. Soc.
%K Acid Amino Conformation Data,Nuclear Magnetic Proteins,Biomolecular,Cation Proteins,Lipid Resonance,Phospholipids,Protein Sequence Sequence,Bacterial Transport bilayers,Models,Molecular,Molecular
%N 25
%P 9299--9302
%R 10.1021/ja4042115
%T The structure of the mercury transporter \MerF\ in phospholipid bilayers: a large conformational rearrangement results from \N\-terminal truncation
%V 135
%X The three-dimensional structure of the 81-residue mercury transporter MerF determined in liquid crystalline phospholipid bilayers under physiological conditions by Rotationally Aligned (RA) solid-state NMR has two long helices, which extend well beyond the bilayer, with a well-defined interhelical loop. Truncation of the N-terminal 12 residues, which are mobile and unstructured when the protein is solubilized in micelles, results in a large structural rearrangement of the protein in bilayers. In the full-length protein, the N-terminal helix is aligned nearly parallel to the membrane normal and forms an extension of the first transmembrane helix. By contrast, this helix adopts a perpendicular orientation in the truncated protein. The close spatial proximity of the two Cys-containing metal binding sites in the three-dimensional structure of full-length MerF provides insights into possible transport mechanisms. These results demonstrate that major changes in protein structure can result from differences in amino acid sequence (e.g., full-length vs truncated proteins) as well as the use of a non-native membrane mimetic environment (e.g., micelles) vs liquid crystalline phospholipid bilayers. They provide further evidence of the importance of studying unmodified membrane proteins in near-native bilayer environments in order to obtain accurate structures that can be related to their functions.
@article{lu_structure_2013,
abstract = {The three-dimensional structure of the 81-residue mercury transporter MerF determined in liquid crystalline phospholipid bilayers under physiological conditions by Rotationally Aligned (RA) solid-state NMR has two long helices, which extend well beyond the bilayer, with a well-defined interhelical loop. Truncation of the N-terminal 12 residues, which are mobile and unstructured when the protein is solubilized in micelles, results in a large structural rearrangement of the protein in bilayers. In the full-length protein, the N-terminal helix is aligned nearly parallel to the membrane normal and forms an extension of the first transmembrane helix. By contrast, this helix adopts a perpendicular orientation in the truncated protein. The close spatial proximity of the two Cys-containing metal binding sites in the three-dimensional structure of full-length MerF provides insights into possible transport mechanisms. These results demonstrate that major changes in protein structure can result from differences in amino acid sequence (e.g., full-length vs truncated proteins) as well as the use of a non-native membrane mimetic environment (e.g., micelles) vs liquid crystalline phospholipid bilayers. They provide further evidence of the importance of studying unmodified membrane proteins in near-native bilayer environments in order to obtain accurate structures that can be related to their functions.},
added-at = {2017-03-14T02:48:56.000+0100},
author = {Lu, George J and Tian, Ye and Vora, Nemil and Marassi, Francesca M and Opella, Stanley J},
biburl = {https://www.bibsonomy.org/bibtex/2a7820582ee633d1a65eacb45e3d7d6e6/nmrresource},
doi = {10.1021/ja4042115},
interhash = {67860b764774fcac38733c369d3ff5d3},
intrahash = {a7820582ee633d1a65eacb45e3d7d6e6},
issn = {1520-5126},
journal = {J. Am. Chem. Soc.},
keywords = {Acid Amino Conformation Data,Nuclear Magnetic Proteins,Biomolecular,Cation Proteins,Lipid Resonance,Phospholipids,Protein Sequence Sequence,Bacterial Transport bilayers,Models,Molecular,Molecular},
month = jun,
number = 25,
pages = {9299--9302},
pmid = {23763519},
shorttitle = {The structure of the mercury transporter {\{}MerF{\}} in},
timestamp = {2017-03-14T02:49:21.000+0100},
title = {{The structure of the mercury transporter {\{}MerF{\}} in phospholipid bilayers: a large conformational rearrangement results from {\{}N{\}}-terminal truncation}},
volume = 135,
year = 2013
}