Ionic interactions promote transmembrane helix-helix association depending on sequence context.
Folding and oligomerization of integral membrane proteins frequently depend on specific interactions of transmembrane helices. Interacting amino acids of helix-helix interfaces may form complex motifs and exert different types of molecular forces. Here, a set of strongly self-interacting transmembrane domains (TMDs), as isolated from a combinatorial library, was found to contain basic and acidic residues, in combination with polar nonionizable amino acids and C-terminal GxxxG motifs. Mutational analyses of selected sequences and reconstruction of high-affinity interfaces confirmed the cooperation of these residues in homotypic interactions. Probing heterotypic interaction indicated the presence of interhelical charge-charge interactions. Furthermore, simple motifs of an ionizable residue and GxxxG are significantly overrepresented in natural TMDs, and a specific combination of these motifs exhibits high-affinity heterotypic interaction. We conclude that intramembrane charge-charge interactions depend on sequence context. Moreover, they appear important for homotypic and heterotypic interactions of numerous natural TMDs.
Herrmann
Jana R
JR
Lehrstuhl für Chemie der Biopolymere, Department für biowissenschaftliche Grundlagen, Technische Universität München, Freising, Germany.
Fuchs
Angelika
A
Panitz
Johanna C
JC
Eckert
Thomas
T
Unterreitmeier
Stephanie
S
Frishman
Dmitrij
D
Langosch
Dieter
D
D000595:Amino Acid Sequence / Q000235:genetics / Q000502:physiology*; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D016384:Consensus Sequence / Q000235:genetics; D007477:Ions / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D025941:Protein Interaction Mapping / Q000379:methods; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity / Q000235:genetics
D007477:Ions; D008565:Membrane Proteins; D050505:Mutant Proteins; D011994:Recombinant Proteins