Abstract:
:This review is concerned with the structures and mechanisms of a superfamily of regulatory GTP hydrolases (G proteins). G proteins include Ras and its close homologs, translation elongation factors, and heterotrimeric G proteins. These proteins share a common structural core, exemplified by that of p21ras (Ras), and significant sequence identity, suggesting a common evolutionary origin. Three-dimensional structures of members of the G protein superfamily are considered in light of other biochemical findings about the function of these proteins. Relationships among G protein structures are discussed, and factors contributing to their low intrinsic rate of GTP hydrolysis are considered. Comparison of GTP- and GDP-bound conformations of G proteins reveals how specific contacts between the gamma-phosphate of GTP and the switch II region stabilize potential effector-binding sites and how GTP hydrolysis results in collapse (or reordering) of these surfaces. A GTPase-activating protein probably binds to and stabilizes the conformation of its cognate G protein that recognizes the transition state for hydrolysis, and may insert a catalytic residue into the G protein active site. Inhibitors of nucleotide release, such as the beta gamma subunit of a heterotrimeric G protein, bind selectively to and stabilize the GDP-bound state. Release factors, such as the translation elongation factor, Ts, also recognize the switch regions and destabilize the Mg(2+)-binding site, thereby promoting GDP release. G protein-coupled receptors are expected to operate by a somewhat different mechanism, given that the GDP-bound form of many G protein alpha subunits does not contain bound Mg2+.
journal_name
Annu Rev Biochemjournal_title
Annual review of biochemistryauthors
Sprang SRdoi
10.1146/annurev.biochem.66.1.639subject
Has Abstractpub_date
1997-01-01 00:00:00pages
639-78eissn
0066-4154issn
1545-4509journal_volume
66pub_type
杂志文章,评审abstract::Clathrin-mediated endocytosis (CME) is the major endocytic pathway in mammalian cells. It is responsible for the uptake of transmembrane receptors and transporters, for remodeling plasma membrane composition in response to environmental changes, and for regulating cell surface signaling. CME occurs via the assembly an...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-062917-012644
更新日期:2018-06-20 00:00:00
abstract::Decades of studies have established translation as a multistep, multicomponent process that requires intricate communication to achieve high levels of speed, accuracy, and regulation. A crucial next step in understanding translation is to reveal the functional significance of the large-scale motions implied by static ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.77.070606.101431
更新日期:2008-01-01 00:00:00
abstract::Regulation of gene transcription is vitally important for the maintenance of normal cellular homeostasis. Failure to correctly regulate gene expression, or to deal with problems that arise during the transcription process, can lead to cellular catastrophe and disease. One of the ways cells cope with the challenges of ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-052110-120012
更新日期:2012-01-01 00:00:00
abstract::This review focuses on molecular mechanisms that underlie the communication between the nuclear and mitochondrial genomes in eukaryotic cells. These genomes interact in at least two ways. First, they contribute essential subunit polypeptides to important mitochondrial proteins; second, they collaborate in the synthesi...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.65.070196.003023
更新日期:1996-01-01 00:00:00
abstract::A broad view is given of photoregulated processes as they occur in algae, fungi, halophilic bacteria, higher plants, invertebrates, and higher animals. Emphasis is on the following: the organs, tissues, and organelles that participate; the nature of the photoreceptor pigments; the light-induced structural changes that...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.45.070176.001411
更新日期:1976-01-01 00:00:00
abstract::Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usually conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-060614-034516
更新日期:2015-01-01 00:00:00
abstract::A childhood fascination with animals, plants, and insects was aided and abetted by many giants, beginning with my parents. The Bronx High School of Science and the City College of New York (CCNY) made a solid and priceless grounding in chemistry and biology available free of charge. Abe Mazur at CCNY revealed the wond...
journal_title:Annual review of biochemistry
pub_type: 传,历史文章,杂志文章
doi:10.1146/annurev.biochem.72.081902.140918
更新日期:2003-01-01 00:00:00
abstract::The peptidoglycan biosynthetic pathway is a critical process in the bacterial cell and is exploited as a target for the design of antibiotics. This pathway culminates in the production of the peptidoglycan layer, which is composed of polymerized glycan chains with cross-linked peptide substituents. This layer forms th...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-061809-112742
更新日期:2012-01-01 00:00:00
abstract::Telomeres are essential for genome stability in all eukaryotes. Changes in telomere functions and the associated chromosomal abnormalities have been implicated in human aging and cancer. Telomeres are composed of repetitive sequences that can be maintained by telomerase, a complex containing a reverse transcriptase (h...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.73.071403.160049
更新日期:2004-01-01 00:00:00
abstract::The majority of cellular energy in the form of adenosine triphosphate (ATP) is synthesized by the ubiquitous F(1)F(0) ATP synthase. Power for ATP synthesis derives from an electrochemical proton (or Na(+)) gradient, which drives rotation of membranous F(0) motor components. Efficient rotation not only requires a signi...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.78.081307.104803
更新日期:2009-01-01 00:00:00
abstract::Endocytic mechanisms control the lipid and protein composition of the plasma membrane, thereby regulating how cells interact with their environments. Here, we review what is known about mammalian endocytic mechanisms, with focus on the cellular proteins that control these events. We discuss the well-studied clathrin-m...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.78.081307.110540
更新日期:2009-01-01 00:00:00
abstract::Several genes have been identified for monogenic disorders that variably resemble Parkinson's disease. Dominant mutations in the gene encoding alpha-synuclein enhance the propensity of this protein to aggregate. As a consequence, these patients have a widespread disease with protein inclusion bodies in several brain a...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.74.082803.133400
更新日期:2005-01-01 00:00:00
abstract::Protein folding in the cell is mediated by an extensive network of >1,000 chaperones, quality control factors, and trafficking mechanisms collectively termed the proteostasis network. While the components and organization of this network are generally well established, our understanding of how protein-folding problems...
journal_title:Annual review of biochemistry
pub_type: 杂志文章
doi:10.1146/annurev-biochem-013118-111552
更新日期:2020-06-20 00:00:00
abstract::Prenylation is a class of lipid modification involving covalent addition of either farnesyl (15-carbon) or geranylgeranyl (20-carbon) isoprenoids to conserved cysteine residues at or near the C-terminus of proteins. Known prenylated proteins include fungal mating factors, nuclear lamins, Ras and Ras-related GTP-bindin...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.65.070196.001325
更新日期:1996-01-01 00:00:00
abstract::Mitochondria are essential organelles with numerous functions in cellular metabolism and homeostasis. Most of the >1,000 different mitochondrial proteins are synthesized as precursors in the cytosol and are imported into mitochondria by five transport pathways. The protein import machineries of the mitochondrial membr...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-060815-014352
更新日期:2017-06-20 00:00:00
abstract::The existence and function of actin in the nucleus has been hotly debated for forty years. Recently, beta-actin was found to be a component of mammalian SWI/SNF-like BAF chromatin remodeling complexes and still more recently other SWI/SNF-related chromatin remodeling complexes in yeast, flies, and man. Although the fu...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.71.110601.135507
更新日期:2002-01-01 00:00:00
abstract::To dampen proteotoxic stresses and maintain protein homeostasis, organisms possess a stress-responsive molecular machinery that detects and neutralizes protein damage. A prominent feature of stressed cells is the increased synthesis of heat shock proteins (Hsps) that aid in the refolding of misfolded peptides and rest...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-060809-095203
更新日期:2011-01-01 00:00:00
abstract::Magic angle spinning (MAS) NMR studies of amyloid and membrane proteins and large macromolecular complexes are an important new approach to structural biology. However, the applicability of these experiments, which are based on (13)C- and (15)N-detected spectra, would be enhanced if the sensitivity were improved. Here...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-060614-034206
更新日期:2015-01-01 00:00:00
abstract::Several lines of experimentation suggest that endogenous retinoids, metabolites of vitamin A, play a role in the anterior/posterior development of the central body axis and the limbs of vertebrates. High levels of endogenous retinoids have been detected in proximity to these developing axes in a variety of vertebrate ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.64.070195.001221
更新日期:1995-01-01 00:00:00
abstract::SELEX is a technology for the identification of high affinity oligonucleotide ligands. Large libraries of random sequence single-stranded oligonucleotides, whether RNA or DNA, can be thought of conformationally not as short strings but rather as sequence dependent folded structures with high degrees of molecular rigid...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.64.070195.003555
更新日期:1995-01-01 00:00:00
abstract::Homologous recombination (HR) serves to eliminate deleterious lesions, such as double-stranded breaks and interstrand crosslinks, from chromosomes. HR is also critical for the preservation of replication forks, for telomere maintenance, and chromosome segregation in meiosis I. As such, HR is indispensable for the main...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.77.061306.125255
更新日期:2008-01-01 00:00:00
abstract::Histone proteins are subject to a host of posttranslational modifications (PTMs) that modulate chromatin structure and function. Such control is achieved by the direct alteration of the intrinsic physical properties of the chromatin fiber or by regulating the recruitment and activity of a host of trans-acting nuclear ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-060614-034429
更新日期:2015-01-01 00:00:00
abstract::Proton transfer in the bacterial RC associated with the reduction of the bound QB to the dihydroquinone is an important step in the energetics of photosynthetic bacteria. The binding of two protons by the quinone is associated with the transfer of the second electron to QB at a rate of ca. 10(3) s-1 (pH 7). Mutation o...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.61.070192.004241
更新日期:1992-01-01 00:00:00
abstract::The determination of several structures of nuclear receptor ligand binding domains (LBD) has led to new insights into the mechanism of action of this very important class of receptors. This review describes and compares the different LBD structures and their relationship to the function of the nuclear receptors. The r...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.68.1.559
更新日期:1999-01-01 00:00:00
abstract::Alterations of chromatin structure have been shown to be crucial for response to cell signaling and for programmed gene expression in development. Posttranslational histone modifications influence changes in chromatin structure both directly and by targeting or activating chromatin-remodeling complexes. Histone modifi...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-061809-175347
更新日期:2011-01-01 00:00:00
abstract::Microtubules are polymers that are essential for, among other functions, cell transport and cell division in all eukaryotes. The regulation of the microtubule system includes transcription of different tubulin isotypes, folding of /¿-tubulin heterodimers, post-translation modification of tubulin, and nucleotide-based ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.69.1.277
更新日期:2000-01-01 00:00:00
abstract::I was born in China and would have remained there but for the tumultuous events that led many of my generation to the United States for graduate studies. Norman Davidson introduced me to DNA when I became a postdoctoral fellow in his group at the California Institute of Technology in 1964, and a fortuitous conversatio...
journal_title:Annual review of biochemistry
pub_type: 传,历史文章,杂志文章
doi:10.1146/annurev.biochem.78.030107.090101
更新日期:2009-01-01 00:00:00
abstract::The lipid A moiety of lipopolysaccharide forms the outer monolayer of the outer membrane of most gram-negative bacteria. Escherichia coli lipid A is synthesized on the cytoplasmic surface of the inner membrane by a conserved pathway of nine constitutive enzymes. Following attachment of the core oligosaccharide, nascen...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.76.010307.145803
更新日期:2007-01-01 00:00:00
abstract::The base excision repair pathway is an organism's primary defense against mutations induced by oxidative, alkylating, and other DNA-damaging agents. This pathway is initiated by DNA glycosylases that excise the damaged base by cleavage of the glycosidic bond between the base and the DNA sugar-phosphate backbone. A sub...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.68.1.255
更新日期:1999-01-01 00:00:00
abstract::Multistep 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 multifunct...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.69.1.961
更新日期:2000-01-01 00:00:00