Sequence context strongly modulates association of polar residues in transmembrane helices.
Polar residues are capable of mediating the association of membrane-embedded helices through the formation of side-chain/side-chain inter-helical hydrogen bonds. However, the extent to which native van der Waals packing of the residues surrounding the polar locus can enhance, or interfere with, the interaction of polar residues has not yet been studied. We examined the propensities of four polar residues (aspartic acid, asparagine, glutamic acid, and glutamine) to promote self-association of transmembrane (TM) domains in several biologically derived sequence environments, including (i). four naturally occurring TM domains that contain a Glu or Gln residue (Tnf5/CD40 ligand, C79a/Ig-alpha, C79b/Ig-beta, and Fut3/alpha-fucosyltransferase); and (ii). variants of bacteriophage M13 major coat protein TM segment with Asp and Asn at interfacial and non-interfacial positions. Self-association was quantified by the TOXCAT assay, which measures TM helix self-oligomerization in the Escherichia coli inner membrane. While an appropriately placed polar residue was found in several cases to significantly stabilize TM helix-helix interactions through the formation of an interhelical hydrogen bond, in other cases the strongly polar residues did not enhance the association of the two helices. Overall, these results suggest that an innate structural mechanism may operate to control non-specific association of membrane-embedded polar residues.
Dawson
Jessica P
JP
Department of Molecular Biophysics and Biochemistry, Yale University, Bass Centre Room 420A, 266 Whitney Avenue, New Haven, CT 06520-8114, USA.
Melnyk
Roman A
RA
Deber
Charles M
CM
Engelman
Donald M
DM
D000595:Amino Acid Sequence; D024342:Amino Acids, Acidic / Q000737:chemistry*; D024361:Amino Acids, Basic / Q000737:chemistry*; D001216:Asparagine; D001224:Aspartic Acid; D002213:Capsid / Q000737:chemistry; D036022:Capsid Proteins; D018698:Glutamic Acid; D005973:Glutamine; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D024342:Amino Acids, Acidic; D024361:Amino Acids, Basic; D036022:Capsid Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C025668:coat protein, Bacteriophage M13; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D001216:Asparagine