Lipid-Protein Interplay in Dimerization of Juxtamembrane Domains of Epidermal Growth Factor Receptor

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2018 Mar 1

PMID 29490249

Citations 17

Authors

Ryo Maeda

Takeshi Sato

Kenji Okamoto

Masataka Yanagawa

Yasushi Sako

Affiliations

Soon will be listed here.

Abstract

Transmembrane (TM) helix and juxtamembrane (JM) domains (TM-JM) bridge the extracellular and intracellular domains of single-pass membrane proteins, including epidermal growth factor receptor (EGFR). TM-JM dimerization plays a crucial role in regulation of EGFR kinase activity at the cytoplasmic side. Although the interaction of JM with membrane lipids is thought to be important to turn on EGF signaling, and phosphorylation of Thr654 on JM leads to desensitization, the underlying kinetic mechanisms remain unclear. In particular, how Thr654 phosphorylation regulates EGFR activity is largely unknown. Here, combining single-pair FRET imaging and nanodisc techniques, we showed that phosphatidylinositol 4,5-bis phosphate (PIP) facilitated JM dimerization effectively. We also found that Thr654 phosphorylation dissociated JM dimers in the membranes containing acidic lipids, suggesting that Thr654 phosphorylation electrostatically prevented the interaction with basic residues in JM and acidic lipids. Based on the single-molecule experiment, we clarified the kinetic pathways of the monomer (inactive state)-to-dimer (active state) transition of JM domains and alteration in the pathways depending on the membrane lipid species and Thr654 phosphorylation.

Citing Articles

Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes.

Kumar Singh P, Rybak J, Schuck R, Sahoo A, Buck M, Barrera F Sci Adv. 2024; 10(49):eadl0649.

PMID: 39630914 PMC: 11616708. DOI: 10.1126/sciadv.adl0649.

Bilateral regulation of EGFR activity and local PI(4,5)P dynamics in mammalian cells observed with superresolution microscopy.

Abe M, Yanagawa M, Hiroshima M, Kobayashi T, Sako Y Elife. 2024; 13.

PMID: 39513999 PMC: 11548882. DOI: 10.7554/eLife.101652.

Single molecule tracking based drug screening.

Watanabe D, Hiroshima M, Yasui M, Ueda M Nat Commun. 2024; 15(1):8975.

PMID: 39420015 PMC: 11486946. DOI: 10.1038/s41467-024-53432-w.

Biochemical Pathways Delivering Distinct Glycosphingolipid Patterns in MDA-MB-231 and MCF-7 Breast Cancer Cells.

Markotic A, Omerovic J, Marijan S, Rezic-Muzinic N, culic V Curr Issues Mol Biol. 2024; 46(9):10200-10217.

PMID: 39329960 PMC: 11430773. DOI: 10.3390/cimb46090608.

The prolactin receptor scaffolds Janus kinase 2 via co-structure formation with phosphoinositide-4,5-bisphosphate.

Araya-Secchi R, Bugge K, Seiffert P, Petry A, Haxholm G, Lindorff-Larsen K Elife. 2023; 12.

PMID: 37232489 PMC: 10260020. DOI: 10.7554/eLife.84645.

References

Michailidis I, Rusinova R, Georgakopoulos A, Chen Y, Iyengar R, Robakis N . Phosphatidylinositol-4,5-bisphosphate regulates epidermal growth factor receptor activation. Pflugers Arch. 2010; 461(3):387-97. PMC: 3281421. DOI: 10.1007/s00424-010-0904-3. View

Olayioye M, Neve R, Lane H, Hynes N . The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 2000; 19(13):3159-67. PMC: 313958. DOI: 10.1093/emboj/19.13.3159. View

Nyati M, Morgan M, Feng F, Lawrence T . Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer. 2006; 6(11):876-85. DOI: 10.1038/nrc1953. View

van Meer G, Voelker D, Feigenson G . Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008; 9(2):112-24. PMC: 2642958. DOI: 10.1038/nrm2330. View

Okamoto K, Sako Y . Variational Bayes analysis of a photon-based hidden Markov model for single-molecule FRET trajectories. Biophys J. 2012; 103(6):1315-24. PMC: 3446682. DOI: 10.1016/j.bpj.2012.07.047. View

Kojima K, Imamoto Y, Maeda R, Yamashita T, Shichida Y . Rod visual pigment optimizes active state to achieve efficient G protein activation as compared with cone visual pigments. J Biol Chem. 2013; 289(8):5061-73. PMC: 3931065. DOI: 10.1074/jbc.M113.508507. View

Pirchi M, Ziv G, Riven I, Cohen S, Zohar N, Barak Y . Single-molecule fluorescence spectroscopy maps the folding landscape of a large protein. Nat Commun. 2011; 2:493. PMC: 3209527. DOI: 10.1038/ncomms1504. View

Li H, Panina S, Kaur A, Ruano M, Sanchez-Gonzalez P, la Cour J . Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin. J Biol Chem. 2011; 287(5):3273-81. PMC: 3270982. DOI: 10.1074/jbc.M111.317529. View

Jura N, Endres N, Engel K, Deindl S, Das R, Lamers M . Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment. Cell. 2009; 137(7):1293-307. PMC: 2814540. DOI: 10.1016/j.cell.2009.04.025. View

10.

Imamoto Y, Kojima K, Oka T, Maeda R, Shichida Y . Helical rearrangement of photoactivated rhodopsin in monomeric and dimeric forms probed by high-angle X-ray scattering. Photochem Photobiol Sci. 2015; 14(11):1965-73. DOI: 10.1039/c5pp00175g. View

11.

Lelimousin M, Limongelli V, Sansom M . Conformational Changes in the Epidermal Growth Factor Receptor: Role of the Transmembrane Domain Investigated by Coarse-Grained MetaDynamics Free Energy Calculations. J Am Chem Soc. 2016; 138(33):10611-22. PMC: 5010359. DOI: 10.1021/jacs.6b05602. View

12.

Aifa S, Frikha F, Miled N, Johansen K, Lundstrom I, Svensson S . Phosphorylation of Thr654 but not Thr669 within the juxtamembrane domain of the EGF receptor inhibits calmodulin binding. Biochem Biophys Res Commun. 2006; 347(2):381-7. DOI: 10.1016/j.bbrc.2006.05.200. View

13.

Hiroshima M, Saeki Y, Okada-Hatakeyama M, Sako Y . Dynamically varying interactions between heregulin and ErbB proteins detected by single-molecule analysis in living cells. Proc Natl Acad Sci U S A. 2012; 109(35):13984-9. PMC: 3435199. DOI: 10.1073/pnas.1200464109. View

14.

Wood E, Truesdale A, McDonald O, Yuan D, Hassell A, Dickerson S . A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res. 2004; 64(18):6652-9. DOI: 10.1158/0008-5472.CAN-04-1168. View

15.

Abd Halim K, Koldso H, Sansom M . Interactions of the EGFR juxtamembrane domain with PIP2-containing lipid bilayers: Insights from multiscale molecular dynamics simulations. Biochim Biophys Acta. 2014; 1850(5):1017-1025. PMC: 4547087. DOI: 10.1016/j.bbagen.2014.09.006. View

16.

Wagner M, Stacey M, Liu B, Pawson T . Molecular mechanisms of SH2- and PTB-domain-containing proteins in receptor tyrosine kinase signaling. Cold Spring Harb Perspect Biol. 2013; 5(12):a008987. PMC: 3839611. DOI: 10.1101/cshperspect.a008987. View

17.

Zhang X, Gureasko J, Shen K, Cole P, Kuriyan J . An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell. 2006; 125(6):1137-49. DOI: 10.1016/j.cell.2006.05.013. View

18.

Ogiso H, Ishitani R, Nureki O, Fukai S, Yamanaka M, Kim J . Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell. 2002; 110(6):775-87. DOI: 10.1016/s0092-8674(02)00963-7. View

19.

Wang Y, Gao J, Guo X, Tong T, Shi X, Li L . Regulation of EGFR nanocluster formation by ionic protein-lipid interaction. Cell Res. 2014; 24(8):959-76. PMC: 4123299. DOI: 10.1038/cr.2014.89. View

20.

Maeda R, Hiroshima M, Yamashita T, Wada A, Nishimura S, Sako Y . Single-molecule observation of the ligand-induced population shift of rhodopsin, a G-protein-coupled receptor. Biophys J. 2014; 106(4):915-24. PMC: 3945020. DOI: 10.1016/j.bpj.2014.01.020. View