Mitochondrial cytochrome bc1 complex performs two functions: It is a respiratory multienzyme complex and it recognizes a mitochondrial targeting presequence. Refined crystal structures of the 11-subunit bc1 complex from bovine heart reveal full views of this bifunctional enzyme. The "Rieske" iron-sulfur protein subunit shows significant conformational changes in different crystal forms, suggesting a new electron transport mechanism of the enzyme. The mitochondrial targeting presequence of the "Rieske" protein (subunit 9) is lodged between the two "core" subunits at the matrix side of the complex. These "core" subunits are related to the matrix processing peptidase, and the structure unveils how mitochondrial targeting presequences are recognized.

(2015) Crystal structure of the anion exchanger domain of human erythrocyte band 3. Science, 350 (6261). pp. 680-684. Permanent WRAP url:

The sporadic form of mitochondrial myopathy is associated with somatic mutations in the cytochrome b gene of mtDNA. This myopathy is one cause of the common and often elusive syndrome of exercise intolerance.

The vacuole-type ATPases (V-ATPases) exist in various intracellular compartments of eukaryotic cells to regulate physiological processes by controlling the acidic environment. The crystal structure of the subunit C of Thermus thermophilus V-ATPase, homologous to eukaryotic subunit d of V-ATPases, has been determined at 1.95-Å resolution and located into the holoenzyme complex structure obtained by single particle analysis as suggested by the results of subunit cross-linking experiments. The result shows that VATPase is substantially longer than the related F-type ATPase, due to the insertion of subunit C between the V 1 (soluble) and the Vo (membrane bound) domains. Subunit C, attached to the Vo domain, seems to have a socket like function in attaching the central-stalk subunits of the V 1 domain. This architecture seems essential for the reversible association͞dissociation of the V 1 and the Vo domains, unique for V-ATPase activity regulation.T he vacuole-type ATPases (V-ATPases) are commonly found in many organisms involved in a variety of physiological processes (1). V-ATPases in eukaryotic cells (eukaryotic VATPases) translocate protons across the membrane consuming ATP. They reside within intracellular compartments, including endosomes, lysosomes, and secretory vesicles, and within plasma membranes of certain cells including renal intercalated cells, osteoclasts, and macrophages. Eukaryotic V-ATPases are responsible for various cell functions including the acidification of intracellular compartments, renal acidification, born resorption, and tumor metastasis (2).V-ATPase and the F-type ATP synthase (F-ATPase) are evolutionary related and share the rotary mechanism coupling ATP synthesis͞hydrolysis and proton translocation across the membrane (2-4). However, these two types of ATPase show significant differences. Reversible association͞dissociation of the V 1 domain (soluble) and the V o domain (membrane bound) is a unique activity regulation mechanism compared to FATPase (Fig. 1). For example, glucose deprivation has been shown to cause a rapid dissociation of the yeast V-ATPase into free V 1 and V o domains, which is reversible and independent of de novo protein synthesis (5, 6). Similar observations have been reported for Manduca sexta and mammalian complexes (7-9). Subunit composition and structure in the stalk region of VATPase, which connects the V o and V 1 domains, are suggested to be significantly different from those in F-ATPase (10) (Fig. 1). Thus, this region is possibly responsible for the association͞ dissociation of the complex.V-ATPases are also found in archaea and some eubacteria (prokaryotic V-ATPases) (11). The V-ATPase from Thermus thermophilus is solely responsible for aerobic ATP synthesis in this bacteria, which lacks F-ATPase (12). The Thermus VATPase is composed of nine different subunits, which are arranged within the atp operon in the order of G-I-L-E-C-F-A-B-D, which encodes proteins with molecular sizes of 13, 71,8,20,35,12, 64, 54, and 25 kDa, respectively (10) (Fig. 1). This A...