The Structure of the Mercury Transporter MerF in Phospholipid Bilayers: A Large Conformational Rearrangement Results From N-terminal Truncation

J Am Chem Soc. 2013 Jun 26;135(25):9299-302. doi: 10.1021/ja4042115. Epub 2013 Jun 17.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Cation Transport Proteins / chemistry*
  • Lipid Bilayers / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Phospholipids / chemistry*
  • Protein Conformation

Substances

  • Bacterial Proteins
  • Cation Transport Proteins
  • Lipid Bilayers
  • Phospholipids
  • mercury transport protein, bacterial