-
FEMS Microbiology Reviews Jul 2008The accurate synthesis of proteins, dictated by the corresponding nucleotide sequence encoded in mRNA, is essential for cell growth and survival. Central to this process... (Review)
Review
The accurate synthesis of proteins, dictated by the corresponding nucleotide sequence encoded in mRNA, is essential for cell growth and survival. Central to this process are the aminoacyl-tRNA synthetases (aaRSs), which provide amino acid substrates for the growing polypeptide chain in the form of aminoacyl-tRNAs. The aaRSs are essential for coupling the correct amino acid and tRNA molecules, but are also known to associate in higher order complexes with proteins involved in processes beyond translation. Multiprotein complexes containing aaRSs are found in all three domains of life playing roles in splicing, apoptosis, viral assembly, and regulation of transcription and translation. An overview of the complexes aaRSs form in all domains of life is presented, demonstrating the extensive network of connections between the translational machinery and cellular components involved in a myriad of essential processes beyond protein synthesis.
Topics: Amino Acyl-tRNA Synthetases; Archaea; Bacteria; Eukaryotic Cells; Multienzyme Complexes; Protein Biosynthesis
PubMed: 18522650
DOI: 10.1111/j.1574-6976.2008.00119.x -
Molecules (Basel, Switzerland) Mar 2021Enzyme engineering is an indispensable tool in the field of synthetic biology, where enzymes are challenged to carry out novel or improved functions. Achieving these... (Review)
Review
Enzyme engineering is an indispensable tool in the field of synthetic biology, where enzymes are challenged to carry out novel or improved functions. Achieving these goals sometimes goes beyond modifying the primary sequence of the enzyme itself. The use of protein or nucleic acid scaffolds to enhance enzyme properties has been reported for applications such as microbial production of chemicals, biosensor development and bioremediation. Key advantages of using these assemblies include optimizing reaction conditions, improving metabolic flux and increasing enzyme stability. This review summarizes recent trends in utilizing genetically encodable scaffolds, developed in line with synthetic biology methodologies, to complement the purposeful deployment of enzymes. Current molecular tools for constructing these synthetic enzyme-scaffold systems are also highlighted.
Topics: Animals; Biocatalysis; Enzyme Stability; Enzymes; Genetic Therapy; Humans; Multienzyme Complexes; Protein Engineering; Synthetic Biology
PubMed: 33806660
DOI: 10.3390/molecules26051389 -
Journal of Molecular Biology Sep 2019Prokaryotic transcription is one of the most studied biological systems, with relevance to many fields including the development and use of antibiotics, the construction... (Review)
Review
Prokaryotic transcription is one of the most studied biological systems, with relevance to many fields including the development and use of antibiotics, the construction of synthetic gene networks, and the development of many cutting-edge methodologies. Here, we discuss recent structural, biochemical, and single-molecule biophysical studies targeting the mechanisms of transcription initiation in bacteria, including the formation of the open complex, the reaction of initial transcription, and the promoter escape step that leads to elongation. We specifically focus on the mechanisms employed by the RNA polymerase holoenzyme with the housekeeping sigma factor σ. The recent progress provides answers to long-held questions, identifies intriguing new behaviours, and opens up fresh questions for the field of transcription.
Topics: Bacteria; DNA, Bacterial; DNA-Directed RNA Polymerases; Multienzyme Complexes; Promoter Regions, Genetic; Sigma Factor; Transcription Initiation, Genetic
PubMed: 31082441
DOI: 10.1016/j.jmb.2019.04.046 -
Essays in Biochemistry Jul 2018The structural biogenesis and functional proficiency of the multiheteromeric complexes forming the mitochondrial oxidative phosphorylation system (OXPHOS) require the... (Review)
Review
The structural biogenesis and functional proficiency of the multiheteromeric complexes forming the mitochondrial oxidative phosphorylation system (OXPHOS) require the concerted action of a number of chaperones and other assembly factors, most of which are specific for each complex. Mutations in a large number of these assembly factors are responsible for mitochondrial disorders, in most cases of infantile onset, typically characterized by biochemical defects of single specific complexes. In fact, pathogenic mutations in complex-specific assembly factors outnumber, in many cases, the repertoire of mutations found in structural subunits of specific complexes. The identification of patients with specific defects in assembly factors has provided an important contribution to the nosological characterization of mitochondrial disorders, and has also been a crucial means to identify a huge number of these proteins in humans, which play an essential role in mitochondrial bioenergetics. The wide use of next generation sequencing (NGS) has led to and will allow the identifcation of additional components of the assembly machinery of individual complexes, mutations of which are responsible for human disorders. The functional studies on patients' specimens, together with the creation and characterization of models, are fundamental to better understand the mechanisms of each of them. A new chapter in this field will be, in the near future, the discovery of mechanisms and actions underlying the formation of supercomplexes, molecular structures formed by the physical, and possibly functional, interaction of some of the individual respiratory complexes, particularly complex I (CI), III (CIII), and IV (CIV).
Topics: Humans; Mitochondrial Diseases; Multienzyme Complexes; Mutation; Oxidative Phosphorylation
PubMed: 30030362
DOI: 10.1042/EBC20170099 -
Journal of Biological Inorganic... Jun 2018Nickel-containing enzymes are diverse in terms of function and active site structure. In many cases, the biosynthesis of the active site depends on accessory proteins... (Review)
Review
Nickel-containing enzymes are diverse in terms of function and active site structure. In many cases, the biosynthesis of the active site depends on accessory proteins which transport and insert the Ni ion. We review and discuss the literature related to the maturation of carbon monoxide dehydrogenases (CODH) which bear a nickel-containing active site consisting of a [Ni-4Fe-4S] center called the C-cluster. The maturation of this center has been much less studied than that of other nickel-containing enzymes such as urease and NiFe hydrogenase. Several proteins present in certain CODH operons, including the nickel-binding proteins CooT and CooJ, still have unclear functions. We question the conception that the maturation of all CODH depends on the accessory protein CooC described as essential for nickel insertion into the active site. The available literature reveals biological variations in CODH active site biosynthesis.
Topics: Aldehyde Oxidoreductases; Catalytic Domain; Iron; Multienzyme Complexes; Nickel; Sulfur
PubMed: 29445873
DOI: 10.1007/s00775-018-1541-0 -
Cell Jan 2005It is now clear that the two broad sets of reactions in the ubiquitin-proteasome system (UPS), the conjugative and degradative steps, are intricately coupled in vivo and... (Review)
Review
It is now clear that the two broad sets of reactions in the ubiquitin-proteasome system (UPS), the conjugative and degradative steps, are intricately coupled in vivo and that there are numerous factors that aid in the handling and delivery of ubiquitylated proteins to the proteasome. The report from Richly et al (2005)[this issue of Cell]) suggests how several of the known players in this process might work together in guiding and delivering some substrates to their final destinations.
Topics: Endoplasmic Reticulum; Multienzyme Complexes; Proteasome Endopeptidase Complex; Protein Folding; Ubiquitin
PubMed: 15652473
DOI: 10.1016/j.cell.2004.12.029 -
Cell Metabolism Nov 2007AMP-activated protein kinase (AMPK) has attracted much attention for its key role in energy homeostasis. Three new papers providing structural information on mammalian...
AMP-activated protein kinase (AMPK) has attracted much attention for its key role in energy homeostasis. Three new papers providing structural information on mammalian and yeast AMPK homologs give insights into the binding of the regulatory nucleotides AMP and ATP and how mutations are associated with cardiac glycogen storage disorders.
Topics: AMP-Activated Protein Kinases; Animals; Humans; Models, Molecular; Multienzyme Complexes; Phosphorylation; Protein Serine-Threonine Kinases; Protein Structure, Secondary
PubMed: 17983576
DOI: 10.1016/j.cmet.2007.10.001 -
EMBO Molecular Medicine Feb 2016The 2016 Louis‐Jeantet Prize for Medicine winner John Diffley tells the story of his path to characterise and understand DNA replication. [Image: see text]
The 2016 Louis‐Jeantet Prize for Medicine winner John Diffley tells the story of his path to characterise and understand DNA replication. [Image: see text]
Topics: Cell Cycle; DNA Replication; Genomic Instability; Multienzyme Complexes
PubMed: 26787652
DOI: 10.15252/emmm.201505965 -
Biochimica Et Biophysica Acta Aug 2000Membrane-bound succinate dehydrogenases (succinate:quinone reductases, SQR) and fumarate reductases (quinol:fumarate reductases, QFR) couple the oxidation of succinate... (Review)
Review
Membrane-bound succinate dehydrogenases (succinate:quinone reductases, SQR) and fumarate reductases (quinol:fumarate reductases, QFR) couple the oxidation of succinate to fumarate to the reduction of quinone to quinol and also catalyse the reverse reaction. SQR (respiratory complex II) is involved in aerobic metabolism as part of the citric acid cycle and of the aerobic respiratory chain. QFR is involved in anaerobic respiration with fumarate as the terminal electron acceptor, and is part of an electron transport chain catalysing the oxidation of various donor substrates by fumarate. QFR and SQR complexes are collectively referred to as succinate:quinone oxidoreductases (EC 1.3.5.1), have very similar compositions and are predicted to share similar structures. The complexes consist of two hydrophilic and one or two hydrophobic, membrane-integrated subunits. The larger hydrophilic subunit A carries covalently bound flavin adenine dinucleotide and subunit B contains three iron-sulphur centres. QFR of Wolinella succinogenes and SQR of Bacillus subtilis contain only one hydrophobic subunit (C) with two haem b groups. In contrast, SQR and QFR of Escherichia coli contain two hydrophobic subunits (C and D) which bind either one (SQR) or no haem b group (QFR). The structure of W. succinogenes QFR has been determined at 2.2 A resolution by X-ray crystallography (C.R.D. Lancaster, A. Kröger, M. Auer, H. Michel, Nature 402 (1999) 377-385). Based on this structure of the three protein subunits and the arrangement of the six prosthetic groups, a pathway of electron transfer from the quinol-oxidising dihaem cytochrome b to the site of fumarate reduction and a mechanism of fumarate reduction was proposed. The W. succinogenes QFR structure is different from that of the haem-less QFR of E. coli, described at 3.3 A resolution (T.M. Iverson, C. Luna-Chavez, G. Cecchini, D.C. Rees, Science 284 (1999) 1961-1966), mainly with respect to the structure of the membrane-embedded subunits and the relative orientations of soluble and membrane-embedded subunits. Also, similarities and differences between QFR transmembrane helix IV and transmembrane helix F of bacteriorhodopsin and their implications are discussed.
Topics: Animals; Binding Sites; Crystallography, X-Ray; Electron Transport; Electron Transport Complex II; Escherichia coli; Flavoproteins; Humans; Iron-Sulfur Proteins; Membrane Potentials; Membrane Proteins; Models, Chemical; Models, Molecular; Molecular Structure; Multienzyme Complexes; Oxidoreductases; Succinate Dehydrogenase; Wolinella
PubMed: 11004459
DOI: 10.1016/s0005-2728(00)00180-8 -
Annual Review of Biophysics 2010Replication of DNA is carried out by the replisome, a multiprotein complex responsible for the unwinding of parental DNA and the synthesis of DNA on each of the two DNA... (Review)
Review
Replication of DNA is carried out by the replisome, a multiprotein complex responsible for the unwinding of parental DNA and the synthesis of DNA on each of the two DNA strands. The impressive speed and processivity with which the replisome duplicates DNA are a result of a set of tightly regulated interactions between the replication proteins. The transient nature of these protein interactions makes it challenging to study the dynamics of the replisome by ensemble-averaging techniques. This review describes single-molecule methods that allow the study of individual replication proteins and their functioning within the replisome. The ability to mechanically manipulate individual DNA molecules and record the dynamic behavior of the replisome while it duplicates DNA has led to an improved understanding of the molecular mechanisms underlying DNA replication.
Topics: Bacteriophages; DNA Replication; DNA-Directed DNA Polymerase; Escherichia coli; Eukaryota; Multienzyme Complexes
PubMed: 20462378
DOI: 10.1146/annurev.biophys.093008.131327