TY - JOUR
T1 - Morphologic determinant of tight junctions revealed by claudin-3 structures
AU - Nakamura, Shun
AU - Irie, Katsumasa
AU - Tanaka, Hiroo
AU - Nishikawa, Kouki
AU - Suzuki, Hiroshi
AU - Saitoh, Yasunori
AU - Tamura, Atsushi
AU - Tsukita, Sachiko
AU - Fujiyoshi, Yoshinori
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research (S), the Japan Agency for Medical Research and Development (AMED), Grants-in-Aid for Scientific Research (A), and Core Research for Evolutional Science and Technology (CREST). The synchrotron radiation experiments were performed at BL41XU in SPring-8 with the approval of the Japan Synchrotron Radiation Research Institute (JASRI Proposal numbers: 2015A1090, 2015B1042, 2016A2697, and 2016B2721) and at BL2S1 at the Aichi Synchrotron Radiation center (Proposal No: 2015N2004, 2015N3003, 2015N6006, 2016N3006, and 2016N4007). We thank the beamline staff for excellent facilities and support.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Tight junction is a cell adhesion apparatus functioning as barrier and/or channel in the paracellular spaces of epithelia. Claudin is the major component of tight junction and polymerizes to form tight junction strands with various morphologies that may correlate with their functions. Here we present the crystal structure of mammalian claudin-3 at 3.6 Å resolution. The third transmembrane helix of claudin-3 is clearly bent compared with that of other subtypes. Structural analysis of additional two mutants with a single mutation representing other subtypes in the third helix indicates that this helix takes a bent or straight structure depending on the residue. The presence or absence of the helix bending changes the positions of residues related to claudin-claudin interactions and affects the morphology and adhesiveness of the tight junction strands. These results evoke a model for tight junction strand formation with different morphologies – straight or curvy strands – observed in native epithelia.
AB - Tight junction is a cell adhesion apparatus functioning as barrier and/or channel in the paracellular spaces of epithelia. Claudin is the major component of tight junction and polymerizes to form tight junction strands with various morphologies that may correlate with their functions. Here we present the crystal structure of mammalian claudin-3 at 3.6 Å resolution. The third transmembrane helix of claudin-3 is clearly bent compared with that of other subtypes. Structural analysis of additional two mutants with a single mutation representing other subtypes in the third helix indicates that this helix takes a bent or straight structure depending on the residue. The presence or absence of the helix bending changes the positions of residues related to claudin-claudin interactions and affects the morphology and adhesiveness of the tight junction strands. These results evoke a model for tight junction strand formation with different morphologies – straight or curvy strands – observed in native epithelia.
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U2 - 10.1038/s41467-019-08760-7
DO - 10.1038/s41467-019-08760-7
M3 - Article
C2 - 30778075
AN - SCOPUS:85061713979
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 816
ER -