Transmembrane helix interactions regulate oligomerization of the receptor tyrosine kinase EphA2.

Autor:	Wirth D; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland, USA., Özdemir E; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland, USA., Wimley WC; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, Louisiana, USA., Pasquale EB; Cancer Metabolism and Microenvironment Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA., Hristova K; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland, USA. Electronic address: kh@jhu.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Jul; Vol. 300 (7), pp. 107441. Date of Electronic Publication: 2024 Jun 03.
DOI:	10.1016/j.jbc.2024.107441
Abstrakt:	The transmembrane helices of receptor tyrosine kinases (RTKs) have been proposed to switch between two different dimeric conformations, one associated with the inactive RTK and the other with the active RTK. Furthermore, recent work has demonstrated that some full-length RTKs are associated into oligomers that are larger than dimers, raising questions about the roles of the TM helices in the assembly and function of these oligomers. Here we probe the roles of the TM helices in the assembly of EphA2 RTK oligomers in the plasma membrane. We employ mutagenesis to evaluate the relevance of a published NMR dimeric structure of the isolated EphA2 TM helix in the context of the full-length EphA2 in the plasma membrane. We use two fluorescence methods, Förster Resonance Energy Transfer and Fluorescence Intensity Fluctuations spectrometry, which yield complementary information about the EphA2 oligomerization process. These studies reveal that the TM helix mutations affect the stability, structure, and size of EphA2 oligomers. However, the effects are multifaceted and point to a more complex role of the TM helix than the one expected from the "TM dimer switch" model. Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu