Dimerization of Neu/Erb2 transmembrane domain is controlled by membrane curvature.
Secondary structures of the proto-oncogenic Neu/ErbB2 transmembrane segment and its mutant analogue have been determined in phospholipids. It is found that the mutated peptide possesses less helical character possibly due to the valine/glutamic acid point mutation. Embedding peptides in lipid systems whose topology can change from small (100-200 A) tumbling objects to bilayer discs of 450 A diameter leads to the finding that coiled-coil interactions are only observed in the presence of a bilayer membrane of low curvature, independent of mutation. This strongly suggests that any event that may change membrane topology can therefore perturb the dimerization/ologomerization and subsequent phosphorylation cascade leading to cell growth or cancer processes.
Khemtémourian
Lucie
L
UMR 5144 MOBIOS, CNRS-Université Bordeaux 1, IECB, 2 rue Robert Escarpit, 33607 Pessac, France.
Buchoux
Sébastien
S
Aussenac
Fabien
F
Dufourc
Erick J
EJ
D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry*; D019281:Dimerization; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008560:Membrane Fluidity; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000648:ultrastructure*
D008051:Lipid Bilayers; D008081:Liposomes; D018719:Erb-b2 Receptor Tyrosine Kinases