Structural basis of leukotriene B4 receptor 1 activation.

ABSTRACT: Leukotriene B4 receptor 1 (BLT1) plays crucial roles in the acute inflammatory responses and is a valuable target for anti-inflammation treatment, however, the mechanism by which leukotriene B4 (LTB4) activates receptor remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structure of the LTB4 -bound human BLT1 in complex with a G_i protein in an active conformation at resolution of 2.91 Å. In combination of molecule dynamics (MD) simulation, docking and site-directed mutagenesis, our structure reveals that a hydrogen-bond network of water molecules and key polar residues is the key molecular determinant for LTB4 binding. We also find that the displacement of residues M101^3.36 and I271^7.39 to the center of receptor, which unlock the ion lo

SUBMITTER: Wang N 

PROVIDER: S-EPMC8894450 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature