- Home
- A-Z Publications
- Annual Review of Biochemistry
- Previous Issues
- Volume 69, 2000
Annual Review of Biochemistry - Volume 69, 2000
Volume 69, 2000
- Review Articles
-
-
-
Aminoacyl-tRNA Synthesis
Michael Ibba, and Dieter SöllVol. 69 (2000), pp. 617–650More Less▪ AbstractAminoacyl-tRNAs are substrates for translation and are pivotal in determining how the genetic code is interpreted as amino acids. The function of aminoacyl-tRNA synthesis is to precisely match amino acids with tRNAs containing the corresponding anticodon. This is primarily achieved by the direct attachment of an amino acid to the corresponding tRNA by an aminoacyl-tRNA synthetase, although intrinsic proofreading and extrinsic editing are also essential in several cases. Recent studies of aminoacyl-tRNA synthesis, mainly prompted by the advent of whole genome sequencing and the availability of a vast body of structural data, have led to an expanded and more detailed picture of how aminoacyl-tRNAs are synthesized. This article reviews current knowledge of the biochemical, structural, and evolutionary facets of aminoacyl-tRNA synthesis.
-
-
-
-
Structure and Function of Hexameric Helicases1
S. S. Patel, and K. M. PichaVol. 69 (2000), pp. 651–697More Less▪ AbstractHelicases are motor proteins that couple the hydrolysis of nucleoside triphosphate (NTPase) to nucleic acid unwinding. The hexameric helicases have a characteristic ring-shaped structure, and all, except the eukaryotic minichromosomal maintenance (MCM) helicase, are homohexamers. Most of the 12 known hexameric helicases play a role in DNA replication, recombination, and transcription. A human genetic disorder, Bloom's syndrome, is associated with a defect in one member of the class of hexameric helicases. Significant progress has been made in understanding the biochemical properties, structures, and interactions of these helicases with DNA and nucleotides. Cooperativity in nucleotide binding was observed in many, and sequential NTPase catalysis has been observed in two proteins, gp4 of bacteriophage T7 and rho of Escherichia coli. The crystal structures of the oligomeric T7 gp4 helicase and the hexamer of RepA helicase show structural features that substantiate the observed cooperativity, and both are consistent with nucleotide binding at the subunit interface. Models are presented that show how sequential NTP hydrolysis can lead to unidirectional and processive translocation. Possible unwinding mechanisms based on the DNA exclusion model are proposed here, termed the wedge, torsional, and helix-destabilizing models.
-
-
-
Clathrin
Vol. 69 (2000), pp. 699–727More Less▪ AbstractClathrin was discovered nearly 25 years ago. Since then, a large number of other proteins that participate in the process by which clathrin-coated vesicles retrieve synaptic membranes or take up endocytic receptors have been identified. The functional relationships among these disparate components remain, in many cases, obscure. High-resolution structures of parts of clathrin, determined by X-ray crystallography, and lower-resolution images of assembled coats, determined by electron cryomicroscopy, now provide the information necessary to integrate various lines of evidence and to design experiments that test specific mechanistic notions. This review summarizes and illustrates the recent structural results and outlines what is known about coated-vesicle assembly in the context of this information.
-
-
-
Mediator of Transcriptional Regulation
Vol. 69 (2000), pp. 729–749More Less▪ AbstractThree lines of evidence have converged on a multiprotein Mediator complex as a conserved interface between gene-specific regulatory proteins and the general transcription apparatus of eukaryotes. Mediator was discovered as an activity required for transcriptional activation in a reconstituted system from yeast. Upon resolution to homogeneity, the activity proved to reside in a 20-protein complex, which could exist in a free state or in a complex with RNA polymerase II, termed holoenzyme. A second line of evidence came from screens in yeast for mutations affecting transcription. Two-thirds of Mediator subunits are encoded by genes revealed by these screens. Five of the genetically defined subunits, termed Srbs, were characterized as interacting with the C-terminal domain of RNA polymerase II in vivo, and were shown to bind polymerase in vitro. A third line of evidence has come recently from studies in mammalian transcription systems. Mammalian counterparts of yeast Mediator were shown to interact with transcriptional activator proteins and to play an essential role in transcriptional regulation.
Mediator evidently integrates and transduces positive and negative regulatory information from enhancers and operators to promoters. It functions directly through RNA polymerase II, modulating its activity in promoter-dependent transcription. Details of the Mediator mechanism remain obscure. Additional outstanding questions include the patterns of promoter-specificity of the various Mediator subunits, the possible cell-type–specificity of Mediator subunit composition, and the full structures of both free Mediator and RNA polymerase II holoenzyme.
-
-
-
Critical Analysis of Antibody Catalysis
Vol. 69 (2000), pp. 751–793More Less▪ AbstractAntibody molecules elicited with rationally designed transition-state analogs catalyze numerous reactions, including many that cannot be achieved by standard chemical methods. Although relatively primitive when compared with natural enzymes, these catalysts are valuable tools for probing the origins and evolution of biological catalysis. Mechanistic and structural analyses of representative antibody catalysts, generated with a variety of strategies for several different reaction types, suggest that their modest efficiency is a consequence of imperfect hapten design and indirect selection. Development of improved transition-state analogs, refinements in immunization and screening protocols, and elaboration of general strategies for augmenting the efficiency of first-generation catalytic antibodies are identified as evident, but difficult, challenges for this field. Rising to these challenges and more successfully integrating programmable design with the selective forces of biology will enhance our understanding of enzymatic catalysis. Further, it should yield useful protein catalysts for an enhanced range of practical applications in chemistry and biology.
-
-
-
GTPase-Activating Proteins for Heterotrimeric G Proteins: Regulators of G Protein Signaling (RGS) and RGS-Like Proteins
Vol. 69 (2000), pp. 795–827More Less▪ AbstractGTPase-activating proteins (GAPs) regulate heterotrimeric G proteins by increasing the rates at which their α subunits hydrolyze bound GTP and thus return to the inactive state. G protein GAPs act allosterically on Gα subunits, in contrast to GAPs for the Ras-like monomeric GTP-binding proteins. Although they do not contribute directly to the chemistry of GTP hydrolysis, G protein GAPs can accelerate hydrolysis >2000-fold. G protein GAPs include both effector proteins (phospholipase C-β, p115RhoGEF) and a growing family of regulators of G protein signaling (RGS proteins) that are found throughout the animal and fungal kingdoms. GAP activity can sharpen the termination of a signal upon removal of stimulus, attenuate a signal either as a feedback inhibitor or in response to a second input, promote regulatory association of other proteins, or redirect signaling within a G protein signaling network. GAPs are regulated by various controls of their cellular concentrations, by complex interactions with Gβγ or with Gβ5 through an endogenous Gγ-like domain, and by interaction with multiple other proteins.
-
-
-
Regulation of Chromosome Replication
Vol. 69 (2000), pp. 829–880More Less▪ AbstractThe initiation of DNA replication in eukaryotic cells is tightly controlled to ensure that the genome is faithfully duplicated once each cell cycle. Genetic and biochemical studies in several model systems indicate that initiation is mediated by a common set of proteins, present in all eukaryotic species, and that the activities of these proteins are regulated during the cell cycle by specific protein kinases. Here we review the properties of the initiation proteins, their interactions with each other, and with origins of DNA replication. We also describe recent advances in understanding how the regulatory protein kinases control the progress of the initiation reaction. Finally, we describe the checkpoint mechanisms that function to preserve the integrity of the genome when the normal course of genome duplication is perturbed by factors that damage the DNA or inhibit DNA synthesis.
-
-
-
Helical Membrane Protein Folding, Stability, and Evolution
Vol. 69 (2000), pp. 881–922More Less▪ AbstractHelical membrane protein folding and oligomerization can be usefully conceptualized as involving two energetically distinct stages—the formation and subsequent side-to-side association of independently stable transbilayer helices. The interactions of helices with the bilayer, with prosthetic groups, and with each other are examined in the context of recent evidence. We conclude that the two-stage concept remains useful as an approach to simplifying discussions of stability, as a framework for folding concepts, and as a basis for understanding membrane protein evolution.
-
-
-
Synthesis of Native Proteins by Chemical Ligation*
Vol. 69 (2000), pp. 923–960More Less▪ AbstractIn just a few short years, the chemical ligation of unprotected peptide segments in aqueous solution has established itself as the most practical method for the total synthesis of native proteins. A wide range of proteins has been prepared. These synthetic molecules have led to the elucidation of gene function, to the discovery of novel biology, and to the determination of new three-dimensional protein structures by both NMR and X-ray crystallography. The facile access to novel analogs provided by chemical protein synthesis has led to original insights into the molecular basis of protein function in a number of systems. Chemical protein synthesis has also enabled the systematic development of proteins with enhanced potency and specificity as candidate therapeutic agents.
-
-
-
Swinging Arms and Swinging Domains in Multifunctional Enzymes: Catalytic Machines for Multistep Reactions
Vol. 69 (2000), pp. 961–1004More Less▪ AbstractMultistep chemical reactions are increasingly seen as important in a growing number of complex biotransformations. Covalently attached prosthetic groups or swinging arms, and their associated protein domains, are essential to the mechanisms of active-site coupling and substrate channeling in a number of the multifunctional enzyme systems responsible. The protein domains, for which the posttranslational machinery in the cell is highly specific, are crucially important, contributing to the processes of molecular recognition that define and protect the substrates and the catalytic intermediates. The domains have novel folds and move by virtue of conformationally flexible linker regions that tether them to other components of their respective multienzyme complexes. Structural and mechanistic imperatives are becoming apparent as the assembly pathways and the coupling of multistep reactions catalyzed by these dauntingly complex molecular machines are unraveled.
-
-
-
Structure and Function of Cytochrome bc Complexes
Vol. 69 (2000), pp. 1005–1075More Less▪ AbstractThe cytochrome bc complexes represent a phylogenetically diverse group of complexes of electron-transferring membrane proteins, most familiarly represented by the mitochondrial and bacterial bc1 complexes and the chloroplast and cyanobacterial b6f complex. All these complexes couple electron transfer to proton translocation across a closed lipid bilayer membrane, conserving the free energy released by the oxidation-reduction process in the form of an electrochemical proton gradient across the membrane. Recent exciting developments include the application of site-directed mutagenesis to define the role of conserved residues, and the emergence over the past five years of X-ray structures for several mitochondrial complexes, and for two important domains of the b6f complex.
-
Previous Volumes
-
Volume 93 (2024)
-
Volume 92 (2023)
-
Volume 91 (2022)
-
Volume 90 (2021)
-
Volume 89 (2020)
-
Volume 88 (2019)
-
Volume 87 (2018)
-
Volume 86 (2017)
-
Volume 85 (2016)
-
Volume 84 (2015)
-
Volume 83 (2014)
-
Volume 82 (2013)
-
Volume 81 (2012)
-
Volume 80 (2011)
-
Volume 79 (2010)
-
Volume 78 (2009)
-
Volume 77 (2008)
-
Volume 76 (2007)
-
Volume 75 (2006)
-
Volume 74 (2005)
-
Volume 73 (2004)
-
Volume 72 (2003)
-
Volume 71 (2002)
-
Volume 70 (2001)
-
Volume 69 (2000)
-
Volume 68 (1999)
-
Volume 67 (1998)
-
Volume 66 (1997)
-
Volume 65 (1996)
-
Volume 64 (1995)
-
Volume 63 (1994)
-
Volume 62 (1993)
-
Volume 61 (1992)
-
Volume 60 (1991)
-
Volume 59 (1990)
-
Volume 58 (1989)
-
Volume 57 (1988)
-
Volume 56 (1987)
-
Volume 55 (1986)
-
Volume 54 (1985)
-
Volume 53 (1984)
-
Volume 52 (1983)
-
Volume 51 (1982)
-
Volume 50 (1981)
-
Volume 49 (1980)
-
Volume 48 (1979)
-
Volume 47 (1978)
-
Volume 46 (1977)
-
Volume 45 (1976)
-
Volume 44 (1975)
-
Volume 43 (1974)
-
Volume 42 (1973)
-
Volume 41 (1972)
-
Volume 40 (1971)
-
Volume 39 (1970)
-
Volume 38 (1969)
-
Volume 37 (1968)
-
Volume 36 (1967)
-
Volume 35 (1966)
-
Volume 34 (1965)
-
Volume 33 (1964)
-
Volume 32 (1963)
-
Volume 31 (1962)
-
Volume 30 (1961)
-
Volume 29 (1960)
-
Volume 28 (1959)
-
Volume 27 (1958)
-
Volume 26 (1957)
-
Volume 25 (1956)
-
Volume 24 (1955)
-
Volume 23 (1954)
-
Volume 22 (1953)
-
Volume 21 (1952)
-
Volume 20 (1951)
-
Volume 19 (1950)
-
Volume 18 (1949)
-
Volume 17 (1948)
-
Volume 16 (1947)
-
Volume 15 (1946)
-
Volume 14 (1945)
-
Volume 13 (1944)
-
Volume 12 (1943)
-
Volume 11 (1942)
-
Volume 10 (1941)
-
Volume 9 (1940)
-
Volume 8 (1939)
-
Volume 7 (1938)
-
Volume 6 (1937)
-
Volume 5 (1936)
-
Volume 4 (1935)
-
Volume 3 (1934)
-
Volume 2 (1933)
-
Volume 1 (1932)
-
Volume 0 (1932)