ABSTRACT
The orchestration of mitochondria within the cell represents a critical aspect of cell biology. At the center of this process is the outer mitochondrial membrane protein, Miro. Miro coordinates diverse cellular processes by regulating connections between organelles and the cytoskeleton that range from mediating contacts between the endoplasmic reticulum and mitochondria to the regulation of both actin and microtubule motor proteins. Recently, a number of cell biological, biochemical, and protein structure studies have helped to characterize the myriad roles played by Miro. In addition to answering questions regarding Miro's function, these studies have opened the door to new avenues in the study of Miro in the cell. This review will focus on summarizing recent findings for Miro's structure, function, and activity while highlighting key questions that remain unanswered.
Subject(s)
Mitochondria/metabolism , Mitochondrial Membranes/chemistry , Mitochondrial Membranes/metabolism , Mitochondrial Proteins/metabolism , Animals , Humans , Mitochondria/chemistry , Mitochondrial Proteins/chemistry , Models, Molecular , rho GTP-Binding Proteins/chemistry , rho GTP-Binding Proteins/metabolismABSTRACT
Trigger factor is a molecular chaperone that is present in all species of eubacteria. It binds to the ribosomal 50S subunit near the translation exit tunnel and is thought to be the first protein to interact with nascent polypeptides emerging from the ribosome. The chaperone has a peptidyl-prolyl cis-trans isomerase (PPIase) activity that catalyzes the rate-limiting proline isomerization in the protein-folding process. We have determined the crystal structure of nearly full-length trigger factor from Vibrio cholerae by x-ray crystallography at 2.5-A resolution. The structure is composed of two trigger-factor molecules related by a noncrystallographic two-fold symmetry axis. The monomer has an elongated shape and is folded into three domains: an N-terminal domain I that binds to the ribosome, a central domain II that contains PPIase activity, and a C-terminal domain III. The active site of the PPIase domain is occupied by a loop from domain III, suggesting that the PPIase activity of the protein could be regulated. The dimer interface is formed between domains I and III and contains residues of mixed properties. Further implications about dimerization, ribosome binding, and other functions of trigger factor are discussed.
