biostudies-literatureEk Vitorin JFNHLBI NIH HHSNIGMS NIH HHS127-40https://www.ebi.ac.uk/biostudies/studies/S-EPMC4805864biostudies-literatureUnknown110(1)Separate connexin domains partake in proposed gating mechanisms of gap junction channels. The amino-terminus (NT) domains, which contribute to voltage sensing, may line the channel's cytoplasmic-facing funnel surface, stabilize the channel's overall structure through interactions with the transmembrane domains and each other, and integrate to form a compound particle to gate the channel closed. Interactions of the carboxyl-terminus (CT) and cytoplasmic loop (CL) domains underlie voltage- and low pH-triggered channel closure. To elucidate potential cooperation of these gating mechanisms, we replaced the Cx43NT with the Cx37NT (chimera Cx43(∗)NT37), leaving the remainder of the Cx43 sequence, including the CT and CL, unchanged. Compared to wild-type Cx43 (Cx43WT), Cx43(∗)NT37 junctions exhibBiophysical journalDeterminants of Cx43 Channel Gating and Permeation: The Amino Terminus.PMC4805864GM086199R01 HL058732R01 HL131712Pontifex TKBurt JMEk Vitorin JFfalseDeterminants of Cx43 Channel Gating and Permeation: The Amino Terminus.Separate connexin domains partake in proposed gating mechanisms of gap junction channels. The amino-terminus (NT) domains, which contribute to voltage sensing, may line the channel's cytoplasmic-facing funnel surface, stabilize the channel's overall structure through interactions with the transmembrane domains and each other, and integrate to form a compound particle to gate the channel closed. Interactions of the carboxyl-terminus (CT) and cytoplasmic loop (CL) domains underlie voltage- and low pH-triggered channel closure. To elucidate potential cooperation of these gating mechanisms, we replaced the Cx43NT with the Cx37NT (chimera Cx43(∗)NT37), leaving the remainder of the Cx43 sequence, including the CT and CL, unchanged. Compared to wild-type Cx43 (Cx43WT), Cx43(∗)NT37 junctions exhib2016-01-01T00:00:00Z2016 Jan2026-05-05T09:26:38.052Z2019-03-27T03:10:11ZS-EPMC48058642674541610.1016/j.bpj.2015.10.054