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Transmembrane helix-helix interactions between a receptor tyrosine kinase and a viral oncoprotein

Windisch, D.; Bürck, J.; Grage, S.; Ziegler, C.; Ulrich, A.S.

Abstract:
The platelet-derived growth factor receptor (PDGFR) is a receptor tyrosine kinase that gets constitutively activated by the oncogenic E5 protein from papillomavirus, leading to uncontrolled proliferation and cancer. Bovine E5 with a length of only 44 amino acids consists largely of a transmembrane helix that can engage in specific helix-helix interactions with the transmembrane segment of PDGFR [1,2]. Our aim is to elucidate the structural criteria by which these transmembrane segments recognize each other, and to describe the oligomeric bundle formed in the lipid bilayer. We reconstituted each of the two recombinantly expressed polypeptides in lipid bilayers with different acyl chain lengths, in order to (i) confirm their intact helical conformation, to (ii) determine their molecular alignment in the lipid membrane, to (iii) monitor any changes in response to bilayer thickness, and to (iv) observe the structural effect of one partner on the other. Complementary spectroscopic measurements were carried out using solid-state NMR and synchrotron-radiation circular dichroism on macroscopically oriented membrane samples [3,4,5,6]. We
observed that, when reconstituted alone in lipid bilayers, the E5 helix is inserted almost upright in thick membranes, it starts to tilt and gets slightly deformed in moderately thinner bilayers and becomes aggregated in very thin membranes because of hydrophobic mismatch. ... mehr



Zugehörige Institution(en) am KIT Institut für Organische Chemie (IOC)
Institut für Biologische Grenzflächen (IBG)
Publikationstyp Vortrag
Jahr 2015
Sprache Englisch
Identifikator KITopen-ID: 230102978
HGF-Programm 47.02.02 (POF III, LK 01)
Veranstaltung 3rd Workshop of the Helmholtz Association 'Cross Programme Activity Structural Biology', Berlin, Germany, 5th - 6th November 2015
KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft
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