Characterization of the Structure and Intermolecular Interactions between the Connexin40 and Connexin43 Carboxyl-terminal and Cytoplasmic Loop Domains

Autor: Heidi Vitrac, Sarah Brownell, Paul L. Sorgen, Sylvie Chenavas, Admir Kellezi, Gaelle Spagnol, Vincent Forge, Denis Bouvier, Fabien Kieken
Přispěvatelé: University of Nebraska Medical Center, University of Nebraska System, Department of Biochemistry and Molecular Biology, University of Nebraska System-University of Nebraska System, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Eppley Institute for Research in Cancer and Allied Diseases, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Rok vydání: 2009
Předmět:
Cytoplasm
Magnetic Resonance Spectroscopy
Xenopus
PROTEIN
Gating
030204 cardiovascular system & hematology
CX43
Biochemistry
Connexins
Protein Structure
Secondary
0302 clinical medicine
Protein Isoforms
0303 health sciences
Gap junction
Gap Junctions
Hydrogen-Ion Concentration
Small molecule
PH REGULATION
Cell biology
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
Protein Structure and Folding
Second messenger system
EXPRESSION RATIO
ZONULA OCCLUDENS-1
DICHROISM SPECTROSCOPIC DATA
Molecular Sequence Data
Biology
03 medical and health sciences
Animals
Humans
Homomeric
Amino Acid Sequence
Molecular Biology
030304 developmental biology
Sequence Homology
Amino Acid
C-SRC
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
Cell Biology
biology.organism_classification
NMR
Protein Structure
Tertiary
GAP-JUNCTION CHANNELS
Membrane protein
Connexin 43
CELLS
Oocytes
sense organs
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Journal of Biological Chemistry
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (49), pp.34257-34271. ⟨10.1074/jbc.M109.039594⟩
Journal of Biological Chemistry, 2009, 284 (49), pp.34257-34271. ⟨10.1074/jbc.M109.039594⟩
ISSN: 0021-9258
1083-351X
Popis: International audience; Gap junctions are intercellular channels that allow the passage of ions, small molecules, and second messengers that are essential for the coordination of cellular function. They are formed by two hemichannels, each constituted by the oligomerization of six connexins (Cx). Among the 21 different human Cx isoforms, studies have suggested that in the heart, Cx40 and Cx43 can oligomerize to form heteromeric hemichannels. The mechanism of heteromeric channel regulation has not been clearly defined. Tissue ischemia leads to intracellular acidification and closure of Cx43 and Cx40 homomeric channels. However, coexpression of Cx40 and Cx43 in Xenopus oocytes enhances the pH sensitivity of the channel. This phenomenon requires the carboxyl-terminal (CT) part of both connexins. In this study we used different biophysical methods to determine the structure of the Cx40CT and characterize the Cx40CT/Cx43CT interaction. Our results revealed that the Cx40CT is an intrinsically disordered protein similar to the Cx43CT and that the Cx40CT and Cx43CT can interact. Additionally, we have identified an interaction between the Cx40CT and the cytoplasmic loop of Cx40 as well as between the Cx40CT and the cytoplasmic loop of Cx43 (and vice versa). Our studies support the “particle-receptor” model for pH gating of Cx40 and Cx43 gap junction channels and suggest that interactions between cytoplasmic regulatory domains (both homo- and hetero-connexin) could be important for the regulation of heteromeric channels.
Databáze: OpenAIRE
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