1.A.24.1.8
Connexin40 (Cx40; Gap Junction Protein δ4; GJδ4) of 370 aas and 4 TMSs (Kopanic et al. 2015).  A phosphorylatable PDZ-domain-binding motif (PDZbm) at the C-terminus of Cx40 is critical for its trafficking and the ability to form functional GJCs, and it is relevant to pulmonary arterial hypertension (PAH) (Wei, L, personal communication).  Additionally:

• (1)  Conserved interaction clusters: Comparative sequence analysis across connexins identified four conserved residue clusters that underlie distinct functional processes, including subunit stability, gating, hemichannel assembly, and full gap junction channel (GJC) formation.  (2)  Dynamic behavior of clusters: Molecular dynamics (MD) simulations revealed region- and cluster-specific flexibility patterns. Rigid clusters act as structural scaffolds, while flexible regions correspond to functional gating and assembly interfaces.  (3)  MD system development: A new 12-subunit, double-bilayer MD platform for connexin GJCs was established, enabling physiologically realistic simulations of intercellular channels and setting the stage for future drug discovery and mechanistic studies (Shirley Xie, pesonal communication).