title: Molecular and topological membrane folding determinants of transient receptor potential vanilloid 2 channel.
abstract: Transient Receptor Potential (TRP) channels are related to adaptation to the environment and somatosensation. The transient receptor potential vanilloid (TRPV) subfamily includes six closely evolutionary related ion channels sharing the same domain organization and tetrameric arrangement in the membrane. In this study we have characterized biochemically TRPV2 channel membrane protein folding and transmembrane (TM) architecture. Deleting the first N-terminal 74 residues preceding the ankyrin repeat domain (ARD) show a key role for this region in targeting the protein to the membrane. We have demonstrated the co-translational insertion of the membrane-embedded region of the TRPV2 and its disposition in biological membranes, identifying that TM1-TM4 and TM5-TM6 regions can assemble as independent folding domains. The ARD is not required for TM domain insertion in the membrane. The folding features observed for TRPV2 may be conserved and shared among other TRP channels outside the TRPV subfamily.
authors.affiliation: Departament de Bioquímica i de Biologia Molecular, Unitat de Biofísica, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Doñate-Macian
authors.affiliation: Department of Biochemistry and Molecular Biology, ERI BioTecMed, University of Valencia, Dr. Moliner 50, 46100 Burjassot, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Bañó-Polo
authors.affiliation: Departament de Bioquímica i de Biologia Molecular, Unitat de Biofísica, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Vazquez-Ibar
authors.affiliation: Department of Biochemistry and Molecular Biology, ERI BioTecMed, University of Valencia, Dr. Moliner 50, 46100 Burjassot, Spain. Electronic address: Ismael.Mingarro@uv.es.
authors.forename: Ismael
authors.initials: I
authors.lastname: Mingarro
authors.affiliation: Departament de Bioquímica i de Biologia Molecular, Unitat de Biofísica, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain. Electronic address: peralvarezmarin@gmail.com.
authors.forename: Alex
authors.initials: A
authors.lastname: Perálvarez-Marín
mesh_terms: D000818:Animals; D017089:Ankyrin Repeat; D002462:Cell Membrane / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D050916:TRPV Cation Channels; C476722:Trpv2 protein, rat
keywords: Calcium signaling; Ion channels; Membrane protein folding and biogenesis; Membrane protein trafficking; TRP channels