Structural insights into the oligomerization of FtsH periplasmic domain from Thermotoga maritima

摘要

Abstract Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. The transmembrane protein, FtsH, is the only known ATP-dependent protease responsible for this task. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. The structure and function of the ATPase and protease domains of FtsH have been previously characterized while the role of the FtsH periplasmic domain has not clearly identified. Here, we report the 1.5–1.95?? resolution crystal structures of the Thermotoga maritima FtsH periplasmic domain ( tm PD) and describe the dynamic features of tm PD oligomerization. Highlights ? We report the 1.5–1.95A resolution crystal structures of the Thermotoga maritima FtsH periplasmic domain ( tm PD). ? Acidic residues at the pore region of tm PD are highly conserved among only the thermophilic, FtsH homologs. ? The negative charge repulsion of tm PD destabilizes its hexamerization. ? Dynamical features of the PD in hexameric full-length FtsH may be relevant for the substrate recognition.