Abstract
Polar residues in transmembrane alpha-helices may strongly influence the folding or association of integral membrane proteins. To test whether a motif that promotes helix association in a soluble protein could do the same within a membrane, we designed a model transmembrane helix based on the GCN4 leucine zipper. We found in both detergent micelles and biological membranes that helix association is driven strongly by asparagine, independent of the rest of the hydrophobic leucine and/or valine sequence. Hydrogen bonding between membrane helices gives stronger associations than the packing of surfaces in glycophorin A helices, creating an opportunity to stabilize structures, but also implying a danger that non-specific interactions might occur. Thus, membrane proteins may fold to avoid exposure of strongly hydrogen bonding groups at their lipid exposed surfaces.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Asparagine / chemistry
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Cell Membrane / metabolism
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Chloramphenicol O-Acetyltransferase / chemistry
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Chloramphenicol O-Acetyltransferase / genetics
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Chloramphenicol O-Acetyltransferase / metabolism
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Circular Dichroism
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DNA-Binding Proteins*
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Detergents / chemistry
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Dimerization
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Electrophoresis, Polyacrylamide Gel
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Fungal Proteins / chemistry
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Glycophorins / chemistry
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Glycophorins / genetics
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Glycophorins / metabolism
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Hydrogen Bonding
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Leucine Zippers
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Magnetic Resonance Spectroscopy
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Membrane Proteins / chemistry*
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Membrane Proteins / metabolism
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Micelles
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Micrococcal Nuclease / chemistry
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Molecular Sequence Data
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Peptides / chemistry
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Protein Conformation
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Protein Kinases / chemistry
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Protein Structure, Secondary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae Proteins*
Substances
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DNA-Binding Proteins
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Detergents
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Fungal Proteins
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Glycophorins
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Membrane Proteins
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Micelles
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Peptides
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Asparagine
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Chloramphenicol O-Acetyltransferase
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Protein Kinases
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Micrococcal Nuclease