title: Structure of the membrane reconstituted transmembrane-juxtamembrane peptide EGFR(622-660) and its interaction with Ca2+/calmodulin.
abstract: The transmembrane (TM) and juxtamembrane (JM) regions of the epidermal growth factor receptor (EGFR) couple ligand binding in the extracellular domain to activation of the kinase domain. Solid-state NMR and polarized FTIR measurements of peptides corresponding to the TM plus JM regions of EGFR (residues 622-660) reconstituted in model phospholipid membranes are presented to address the role of the short cytoplasmic JM sequence (residues 645-660) in regulating EGFR activity. We show that the TM domain is helical with a transition to non-helical structure at the TM-JM boundary. Fluorescence measurements indicate that the JM region of EGFR(622-660) binds to the membrane surface and that binding can be reversed by the addition of the complex of Ca2+ and calmodulin. Together these data support models suggesting the cytoplasmic JM region of EGFR plays an active role in regulating receptor activity.
authors.affiliation: Department of Biochemistry and Cell Biology, Center for Structural Biology, Stony Brook University, Stony Brook, New York 11794-5215, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sato
authors.forename: Payal
authors.initials: P
authors.lastname: Pallavi
authors.forename: Urszula
authors.initials: U
authors.lastname: Golebiewska
authors.forename: Stuart
authors.initials: S
authors.lastname: McLaughlin
authors.forename: Steven O
authors.initials: SO
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D002247:Carbon Isotopes; D002942:Circular Dichroism; D003903:Deuterium; D019281:Dimerization; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared
chemical_list: D002147:Calmodulin; D002247:Carbon Isotopes; D008024:Ligands; D010446:Peptide Fragments; D003903:Deuterium; D066246:ErbB Receptors; D002118:Calcium