Two GxxxG-like motifs facilitate promiscuous interactions of the human ErbB transmembrane domains.
Members of the ErbB/HER family of epidermal growth factor receptor tyrosine kinases cross a membrane with a single transmembrane (TM) helix. ErbB receptors form diverse homo- and heterodimers, which substantially increases the signaling potential of ErbB receptors. The involvement of the ErbB TM domains in homo- and heterodimerization is largely enigmatic. In this study, we experimentally analyzed the potential role of two conserved GxxxG-like motifs for mediating and/or stabilizing homo- and hetero-oligomeric interactions of the human ErbB TM domains. Both motifs appear to be critical for homo- and hetero-oligomeric TM helix interactions. Consequently, multiple TM structures are possible for the various ErbB homo- and heterodimers, which might be critical for the formation and TM signaling of specific ErbB pairs in vivo.
Institut für Biochemie und Molekularbiologie, ZBMZ, Albert-Ludwigs-Universität, Freiburg, Germany.
Claudia
C
Escher
Florian
F
Cymer
Dirk
D
Schneider
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D020794:Receptor Protein-Tyrosine Kinases