-
Current Opinion in Cell Biology Feb 2010In 1993, an enzyme with an ATP-dependent microtubule-severing activity was purified from sea urchin eggs and named katanin, after the Japanese word for sword. Now we... (Review)
Review
In 1993, an enzyme with an ATP-dependent microtubule-severing activity was purified from sea urchin eggs and named katanin, after the Japanese word for sword. Now we know that katanin, spastin, and fidgetin form a family of closely related microtubule-severing enzymes that is widely distributed in eukaryotes ranging from Tetrahymena and Chlamydomonas to humans. Here we review the diverse in vivo functions of these proteins and the recent significant advances in deciphering the biophysical mechanism of microtubule severing.
Topics: Adenosine Triphosphatases; Amino Acid Sequence; Animals; Humans; Katanin; Microtubule-Associated Proteins; Microtubules; Models, Molecular; Molecular Sequence Data; Phylogeny; Protein Conformation
PubMed: 19963362
DOI: 10.1016/j.ceb.2009.11.001 -
FEBS Letters Sep 2015p97 (also known as Cdc48, Ter94, and VCP) is an essential, abundant and highly conserved ATPase driving the turnover of ubiquitylated proteins in eukaryotes. Even though... (Review)
Review
p97 (also known as Cdc48, Ter94, and VCP) is an essential, abundant and highly conserved ATPase driving the turnover of ubiquitylated proteins in eukaryotes. Even though p97 is involved in highly diverse cellular pathways and processes, it exhibits hardly any substrate specificity on its own. Instead, it relies on a large number of regulatory cofactors controlling substrate specificity and turnover. The complexity as well as temporal and spatial regulation of the interactions between p97 and its cofactors is only beginning to be understood at the molecular level. Here, we give an overview on the structural framework of p97 interactions with its cofactors, the emerging principles underlying the assembly of complexes with different cofactors, and the pathogenic effects of disease-associated p97 mutations on cofactor binding.
Topics: Adenosine Triphosphatases; Amino Acid Sequence; Cell Cycle Proteins; Humans; Models, Molecular; Molecular Sequence Data; Mutation; Protein Binding; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Substrate Specificity; Valosin Containing Protein
PubMed: 26320413
DOI: 10.1016/j.febslet.2015.08.028 -
Biochimica Et Biophysica Acta Mar 2011The vast majority of proteins trafficking across or into the bacterial cytoplasmic membrane occur via the translocon. The translocon consists of the SecYEG complex that... (Review)
Review
The vast majority of proteins trafficking across or into the bacterial cytoplasmic membrane occur via the translocon. The translocon consists of the SecYEG complex that forms an evolutionarily conserved heterotrimeric protein-conducting membrane channel that functions in conjunction with a variety of ancillary proteins. For posttranslational protein translocation, the translocon interacts with the cytosolic motor protein SecA that drives the ATP-dependent stepwise translocation of unfolded polypeptides across the membrane. For the cotranslational integration of membrane proteins, the translocon interacts with ribosome-nascent chain complexes and membrane insertion is coupled to polypeptide chain elongation at the ribosome. These processes are assisted by the YidC and SecDF(yajC) complex that transiently interacts with the translocon. This review summarizes our current understanding of the structure-function relationship of the translocon and its interactions with ancillary components during protein translocation and membrane protein insertion. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.
Topics: Adenosine Triphosphatases; Bacterial Proteins; Membrane Transport Proteins; Protein Transport; SEC Translocation Channels; SecA Proteins; Structure-Activity Relationship
PubMed: 20801097
DOI: 10.1016/j.bbamem.2010.08.016 -
Cell Cycle (Georgetown, Tex.) Mar 2017WRNIP1 interacts with WRN helicase, which is defective in the premature aging disease Werner syndrome. WRNIP1 belongs to the AAA+ ATPase family and is conserved from... (Review)
Review
WRNIP1 interacts with WRN helicase, which is defective in the premature aging disease Werner syndrome. WRNIP1 belongs to the AAA+ ATPase family and is conserved from Escherichia coli to human. The protein contains an ubiquitin-binding zinc finger (UBZ) domain at the N terminus and an ATPase domain in the middle region. In addition to WRN, WRNIP1 interacts with proteins involved in multiple cellular pathways, including RAD18, monoubiquitylated PCNA, DNA polymerase δ, RAD51, and ATMIN. Mgs1, the yeast homolog of WRNIP1, may act downstream of ubiquitylation of PCNA to mobilize DNA polymerase δ. By contrast, the functions of WRNIP1 in higher eukaryotic cells remain obscure, although data regarding the roles of WRNIP1 in DNA transactions have emerged recently. Here, we first describe the functions of Mgs1 in DNA transaction. We then describe various features of WRNIP1 and discuss its possible roles based on recent studies of the function of WRNIP1.
Topics: Adenosine Triphosphatases; Amino Acid Sequence; Animals; DNA; DNA Replication; Genomic Instability; Humans; Models, Biological
PubMed: 28118071
DOI: 10.1080/15384101.2017.1282585 -
Cytogenetic and Genome Research 2015After replication of genomic DNA during the S phase, 2 chromatids hold together longitudinally. When cells enter mitosis, the paired sister chromatids start to condense... (Review)
Review
After replication of genomic DNA during the S phase, 2 chromatids hold together longitudinally. When cells enter mitosis, the paired sister chromatids start to condense and then segregate into individual chromatids except for the centromeric region. Upon attachment of microtubules to the kinetochore, subsequent pulling of the 2 sister chromatids by the spindles towards opposite poles results in 2 completely separated chromatids. Besides more than 100 kinds of kinetochore proteins, several key proteins such as cohesin, separase, shugoshin, and condensin contribute to chromatid cohesion and segregation. Among these proteins, condensin, a protein complex composed of 5 subunits discovered 2 decades ago, has been extensively studied in terms of the maintenance of chromosome morphology as its major function. Recent studies on condensin uncovered its role in chromatid cohesion and segregation, which will be reviewed in this article.
Topics: Adenosine Triphosphatases; Cell Cycle Proteins; Centromere; Chromatids; Chromosomal Proteins, Non-Histone; Chromosome Segregation; DNA-Binding Proteins; Kinetochores; Multiprotein Complexes; Cohesins
PubMed: 26998746
DOI: 10.1159/000444868 -
Current Opinion in Structural Biology Apr 2014Recent work has provided the detailed overall architecture and subunit composition of three subtypes of rotary ATPases. Composite models of F-type, V-type and A-type... (Review)
Review
Recent work has provided the detailed overall architecture and subunit composition of three subtypes of rotary ATPases. Composite models of F-type, V-type and A-type ATPases have been constructed by fitting high-resolution X-ray structures of individual components into electron microscopy derived envelopes of the intact enzymes. Electron cryo-tomography has provided new insights into the supra-molecular arrangement of eukaryotic ATP synthases within mitochondria. An inherent flexibility in rotary ATPases observed by different techniques suggests greater dynamics during operation than previously envisioned. The concerted movement of subunits within the complex might provide means of regulation and information transfer between distant parts of rotary ATPases thereby fine tuning these molecular machines to their cellular environment, while optimizing their efficiency.
Topics: Adenosine Triphosphatases; Molecular Motor Proteins; Protein Multimerization; Protein Structure, Quaternary; Rotation
PubMed: 24878343
DOI: 10.1016/j.sbi.2013.11.013 -
Biopolymers Aug 2016The HSP90 molecular chaperone is involved in the activation and cellular stabilization of a range of 'client' proteins, of which oncogenic protein kinases and nuclear... (Review)
Review
The HSP90 molecular chaperone is involved in the activation and cellular stabilization of a range of 'client' proteins, of which oncogenic protein kinases and nuclear steroid hormone receptors are of particular biomedical significance. Work over the last two decades has revealed a conformational cycle critical to the biological function of HSP90, coupled to an inherent ATPase activity that is regulated and manipulated by many of the co-chaperones proteins with which it collaborates. Pharmacological inhibition of HSP90 ATPase activity results in degradation of client proteins in vivo, and is a promising target for development of new cancer therapeutics. Despite this, the actual function that HSP90s conformationally-coupled ATPase activity provides in its biological role as a molecular chaperone remains obscure. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 594-607, 2016.
Topics: Adenosine Triphosphatases; Animals; HSP90 Heat-Shock Proteins; Humans; Protein Conformation; Proteolysis
PubMed: 26991466
DOI: 10.1002/bip.22835 -
Nature Reviews. Microbiology Nov 2012The conserved general secretion (Sec) pathway carries out most protein export in bacteria and is powered by the essential ATPase SecA. Interestingly, mycobacteria and... (Review)
Review
The conserved general secretion (Sec) pathway carries out most protein export in bacteria and is powered by the essential ATPase SecA. Interestingly, mycobacteria and some Gram-positive bacteria possess two SecA proteins: SecA1 and SecA2. In these species, SecA1 is responsible for exporting most proteins, whereas SecA2 exports only a subset of substrates and is implicated in virulence. However, despite the impressive body of knowledge about the canonical SecA1, less is known concerning SecA2 function. Here, we review our current understanding of the different types of SecA2 systems and outline future directions for their study.
Topics: Adenosine Triphosphatases; Bacteria; Bacterial Physiological Phenomena; Bacterial Proteins; Membrane Transport Proteins; Protein Transport; SEC Translocation Channels; SecA Proteins; Virulence Factors
PubMed: 23000954
DOI: 10.1038/nrmicro2874 -
The Biochemical Journal Oct 2014Copper ATPases, in analogy with other members of the P-ATPase superfamily, contain a catalytic headpiece including an aspartate residue reacting with ATP to form a... (Review)
Review
Copper ATPases, in analogy with other members of the P-ATPase superfamily, contain a catalytic headpiece including an aspartate residue reacting with ATP to form a phosphoenzyme intermediate, and transmembrane helices containing cation-binding sites [TMBS (transmembrane metal-binding sites)] for catalytic activation and cation translocation. Following phosphoenzyme formation by utilization of ATP, bound copper undergoes displacement from the TMBS to the lumenal membrane surface, with no H+ exchange. Although PII-type ATPases sustain active transport of alkali/alkali-earth ions (i.e. Na+, Ca2+) against electrochemical gradients across defined membranes, PIB-type ATPases transfer transition metal ions (i.e. Cu+) from delivery to acceptor proteins and, prominently in mammalian cells, undergo trafficking from/to various membrane compartments. A specific component of copper ATPases is the NMBD (N-terminal metal-binding domain), containing up to six copper-binding sites in mammalian (ATP7A and ATP7B) enzymes. Copper occupancy of NMBD sites and interaction with the ATPase headpiece are required for catalytic activation. Furthermore, in the presence of copper, the NMBD allows interaction with protein kinase D, yielding phosphorylation of serine residues, ATP7B trafficking and protection from proteasome degradation. A specific feature of ATP7A is glycosylation and stabilization on plasma membranes. Cisplatin, a platinum-containing anti-cancer drug, binds to copper sites of ATP7A and ATP7B, and undergoes vectorial displacement in analogy with copper.
Topics: Adenosine Triphosphatases; Animals; Biocatalysis; Cation Transport Proteins; Copper; Humans; Protein Structure, Tertiary
PubMed: 25242165
DOI: 10.1042/BJ20140741 -
Gene May 2016p97 (also known as valosin-containing protein (VCP) in mammals or Cdc48p in Saccharomyces cerevisiae) is an evolutionarily conserved ATPase present in all eukaryotes and... (Review)
Review
p97 (also known as valosin-containing protein (VCP) in mammals or Cdc48p in Saccharomyces cerevisiae) is an evolutionarily conserved ATPase present in all eukaryotes and archaebacteria. In conjunction with a collection of cofactors and adaptors, p97/Cdc48p performs an array of biological functions mostly through modulating the stability of 'client' proteins. Using energy from ATP hydrolysis, p97/Cdc48p segregates these molecules from immobile cellular structures such as protein assemblies, membrane organelles, and chromatin. Consequently, the released polypeptides can be efficiently degraded by the ubiquitin proteasome system or recycled. This review summarizes our current understanding of the structure and function of this essential cellular chaperoning system.
Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Cell Cycle Proteins; Chromatin; Homeostasis; Humans; Hydrolysis; Membrane Fusion; Mice; Molecular Targeted Therapy; Mutation; Neoplasms; Protein Conformation; Saccharomyces cerevisiae Proteins; Valosin Containing Protein
PubMed: 26945625
DOI: 10.1016/j.gene.2016.02.042