Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules.

PubWeight™: 2.77‹?› | Rank: Top 1%

🔗 View Article (PMID 2199064)

Published in Cell on August 10, 1990

Authors

U Krengel1, I Schlichting, A Scherer, R Schumann, M Frech, J John, W Kabsch, E F Pai, A Wittinghofer

Author Affiliations

1: Max-Planck-Institut für medizinische Forschung Abteilung Biophysik, Heidelberg, Federal Republic of Germany.

Articles citing this

Ras oncogenes: split personalities. Nat Rev Mol Cell Biol (2008) 7.91

Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. EMBO J (1997) 6.14

A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science (2013) 3.96

Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell (2012) 3.77

Genomic and biological characterization of exon 4 KRAS mutations in human cancer. Cancer Res (2010) 3.24

Single-molecule imaging analysis of Ras activation in living cells. Proc Natl Acad Sci U S A (2004) 2.84

The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol Cell (2013) 2.79

Septin collar formation in budding yeast requires GTP binding and direct phosphorylation by the PAK, Cla4. J Cell Biol (2004) 2.42

Protein-tyrosine kinases regulate the phosphorylation, protein interactions, subcellular distribution, and activity of p21ras GTPase-activating protein. Mol Cell Biol (1991) 2.40

Ras plasma membrane signalling platforms. Biochem J (2005) 2.15

Ras-catalyzed hydrolysis of GTP: a new perspective from model studies. Proc Natl Acad Sci U S A (1996) 1.97

Hydrolysis of GTP by Sec4 protein plays an important role in vesicular transport and is stimulated by a GTPase-activating protein in Saccharomyces cerevisiae. Mol Cell Biol (1992) 1.90

Human immunodeficiency virus type 1 Nef associates with a member of the p21-activated kinase family. J Virol (1996) 1.69

Allosteric modulation of Ras positions Q61 for a direct role in catalysis. Proc Natl Acad Sci U S A (2010) 1.62

Reovirus oncolysis: the Ras/RalGEF/p38 pathway dictates host cell permissiveness to reovirus infection. Proc Natl Acad Sci U S A (2004) 1.53

Alternative splicing of the human Rab6A gene generates two close but functionally different isoforms. Mol Biol Cell (2000) 1.52

The universally conserved prokaryotic GTPases. Microbiol Mol Biol Rev (2011) 1.47

Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. Cell (2014) 1.40

X-ray crystal structures of transforming p21 ras mutants suggest a transition-state stabilization mechanism for GTP hydrolysis. Proc Natl Acad Sci U S A (1992) 1.34

Bordetella bronchiseptica dermonecrotizing toxin induces reorganization of actin stress fibers through deamidation of Gln-63 of the GTP-binding protein Rho. Proc Natl Acad Sci U S A (1997) 1.33

Transformation efficiency of RasQ61 mutants linked to structural features of the switch regions in the presence of Raf. Structure (2007) 1.26

Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders. Hum Mutat (2010) 1.24

The Saccharomyces cerevisiae CDC25 gene product binds specifically to catalytically inactive ras proteins in vivo. Mol Cell Biol (1992) 1.23

Functional reconstitution of COPI coat assembly and disassembly using chemically defined components. Proc Natl Acad Sci U S A (2003) 1.20

Guanosine triphosphatase stimulation of oncogenic Ras mutants. Proc Natl Acad Sci U S A (1999) 1.20

Biological and structural characterization of a Ras transforming mutation at the phenylalanine-156 residue, which is conserved in all members of the Ras superfamily. Proc Natl Acad Sci U S A (1995) 1.16

Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis. Hum Mol Genet (2014) 1.15

GTP hydrolysis is not important for Ypt1 GTPase function in vesicular transport. Mol Cell Biol (1998) 1.15

Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function. Proc Natl Acad Sci U S A (2013) 1.10

Identification of residues of the H-ras protein critical for functional interaction with guanine nucleotide exchange factors. Mol Cell Biol (1994) 1.09

Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer. J Gastroenterol (2012) 1.08

The biochemistry of ras p21. Biochem J (1991) 1.08

Mutations of Ha-ras p21 that define important regions for the molecular mechanism of the SDC25 C-domain, a guanine nucleotide dissociation stimulator. EMBO J (1992) 1.07

Phosphate-binding loop and Rab GTPase function: mutations at Ser29 and Ala30 of Rab5 lead to loss-of-function as well as gain-of-function phenotype. Biochem J (2001) 1.07

TC21 causes transformation by Raf-independent signaling pathways. Mol Cell Biol (1996) 1.03

Theoretical IR spectroscopy based on QM/MM calculations provides changes in charge distribution, bond lengths, and bond angles of the GTP ligand induced by the Ras-protein. Biophys J (2005) 1.02

Intratumor heterogeneity of K-ras2 mutations in colorectal adenocarcinomas: association with degree of DNA aneuploidy. Am J Pathol (1996) 1.02

GTPase mechanism and function: new insights from systematic mutational analysis of the phosphate-binding loop residue Ala30 of Rab5. Biochem J (2000) 1.02

GTPase domains of ras p21 oncogene protein and elongation factor Tu: analysis of three-dimensional structures, sequence families, and functional sites. Proc Natl Acad Sci U S A (1991) 1.01

Critical role for the Val/Gly86 HLA-DR beta dimorphism in autoantigen presentation to human T cells. Proc Natl Acad Sci U S A (1991) 1.00

Death pathways triggered by activated Ras in cancer cells. Front Biosci (Landmark Ed) (2011) 1.00

Role of proto-oncogene activation in carcinogenesis. Environ Health Perspect (1992) 0.99

Allosteric modulation of Ras-GTP is linked to signal transduction through RAF kinase. J Biol Chem (2010) 0.98

Identification of amino acid residues required for Ras p21 target activation. Mol Cell Biol (1991) 0.97

Activated Ras induces cytoplasmic vacuolation and non-apoptotic death in glioblastoma cells via novel effector pathways. Cell Signal (2006) 0.95

Characterization of mutations affecting the Escherichia coli essential GTPase era that suppress two temperature-sensitive dnaG alleles. J Bacteriol (1997) 0.94

Ab initio study of the role of lysine 16 for the molecular switching mechanism of Ras protein p21. Biophys J (1999) 0.93

Molecular dynamics simulations of Gly-12-->Val mutant of p21(ras): dynamic inhibition mechanism. Biophys J (2001) 0.92

Effects of constitutively active GTPases on fibroblast behavior. Cell Mol Life Sci (2006) 0.91

Quantitative exploration of the molecular origin of the activation of GTPase. Proc Natl Acad Sci U S A (2013) 0.91

Characterization of the hinges of the effector loop in the reaction pathway of the activation of ras-proteins. Kinetics of binding of beryllium trifluoride to V29G and I36G mutants of Ha-ras-p21. Protein Sci (1999) 0.90

Specific K-ras2 mutations in human sporadic colorectal adenomas are associated with DNA near-diploid aneuploidy and inhibition of proliferation. Am J Pathol (1998) 0.90

Differential regulation of macropinocytosis by Abi1/Hssh3bp1 isoforms. PLoS One (2010) 0.89

Distinct subclasses of small GTPases interact with guanine nucleotide exchange factors in a similar manner. Mol Cell Biol (1998) 0.88

Purification and characterization of a mutant DnaB protein specifically defective in ATP hydrolysis. J Bacteriol (1992) 0.88

Nucleotide binding to the G12V-mutant of Cdc42 investigated by X-ray diffraction and fluorescence spectroscopy: two different nucleotide states in one crystal. Protein Sci (1999) 0.87

Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma. Nat Genet (2015) 0.87

Lessons from computer simulations of Ras proteins in solution and in membrane. Biochim Biophys Acta (2013) 0.87

Interaction of GTPase-activating protein with p21ras, measured using a continuous assay for inorganic phosphate release. Biochem J (1992) 0.86

Role of the switch II region in the conformational transition of activation of Ha-ras-p21. Protein Sci (2000) 0.86

Rho5p is involved in mediating the osmotic stress response in Saccharomyces cerevisiae, and its activity is regulated via Msi1p and Npr1p by phosphorylation and ubiquitination. Eukaryot Cell (2008) 0.86

Probing the role of loop 2 in Ras function with unnatural amino acids. Proc Natl Acad Sci U S A (1993) 0.86

Functional interaction between p21rap1A and components of the budding pathway in Saccharomyces cerevisiae. Mol Cell Biol (1992) 0.85

Identification of neurofibromin mutants that exhibit allele specificity or increased Ras affinity resulting in suppression of activated ras alleles. Mol Cell Biol (1996) 0.85

Regulation of atrial natriuretic peptide secretion by a novel Ras-like protein. J Cell Biol (2007) 0.85

A rab protein regulates the localization of secretory granules in AtT-20 cells. Mol Biol Cell (1993) 0.83

The arginine finger of RasGAP helps Gln-61 align the nucleophilic water in GAP-stimulated hydrolysis of GTP. Proc Natl Acad Sci U S A (2001) 0.83

Genetic definition of ras effector elements. Mol Cell Biol (1991) 0.82

Mapping the Conformation Space of Wildtype and Mutant H-Ras with a Memetic, Cellular, and Multiscale Evolutionary Algorithm. PLoS Comput Biol (2015) 0.81

Establishment of stable human fibroblast cell lines constitutively expressing active Rho-GTPases. Protoplasma (2006) 0.81

A switch I mutant of Cdc42 exhibits less conformational freedom. Biochemistry (2011) 0.81

The putative "switch 2" domain of the Ras-related GTPase, Rab1B, plays an essential role in the interaction with Rab escort protein. Mol Biol Cell (1998) 0.80

Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution. Elife (2016) 0.79

Prenylation of a Rab1B mutant with altered GTPase activity is impaired in cell-free systems but not in intact mammalian cells. Biochem J (1996) 0.79

Overview of simulation studies on the enzymatic activity and conformational dynamics of the GTPase Ras. Mol Simul (2014) 0.79

Single somatic ras gene point mutation in soft tissue malignant fibrous histiocytomas. Am J Pathol (1996) 0.78

Novel peptides from the RAS-p21 and p53 proteins for the treatment of cancer. Cancer Ther (2007) 0.78

Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras Isoforms and Wild-Type versus Mutated Proteins. ISRN Oncol (2013) 0.78

Catalysis of GTP Hydrolysis by Small GTPases at Atomic Detail by Integration of X-ray Crystallography, Experimental, and Theoretical IR Spectroscopy. J Biol Chem (2015) 0.77

Elevated levels of STAT1 in Fanconi anemia group A lymphoblasts correlate with the cells' sensitivity to DNA interstrand crosslinking drugs. Haematologica (2013) 0.77

Simultaneous and independent tuning of RhoA and Rac1 activity with orthogonally inducible promoters. Integr Biol (Camb) (2014) 0.76

Kinetic mechanisms of mutation-dependent Harvey Ras activation and their relevance for the development of Costello syndrome. Biochemistry (2013) 0.76

Effect of human activated NRAS on replication of delNS1 H5N1 influenza virus in MDCK cells. Virol J (2011) 0.75

New insights into the molecular mechanism of the Rab GTPase Sec4p activation. BMC Struct Biol (2015) 0.75

Articles by these authors

Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers (1983) 99.69

The P-loop--a common motif in ATP- and GTP-binding proteins. Trends Biochem Sci (1990) 14.55

Monolithic microfabricated valves and pumps by multilayer soft lithography. Science (2000) 14.37

Atomic structure of the actin:DNase I complex. Nature (1990) 11.86

Atomic model of the actin filament. Nature (1990) 11.33

The guanine nucleotide-binding switch in three dimensions. Science (2001) 9.34

Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature (1998) 9.30

The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science (1997) 9.21

Role of translocation in the activation and function of protein kinase B. J Biol Chem (1997) 7.29

Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis. EMBO J (1990) 6.51

Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature (1989) 5.38

A microfabricated fluorescence-activated cell sorter. Nat Biotechnol (1999) 5.00

RanGAP1 induces GTPase activity of nuclear Ras-related Ran. Proc Natl Acad Sci U S A (1994) 4.58

MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene (2007) 4.46

Efficacy of prolonged regimes of oxytetracycline in the treatment of nongonococcal urethritis. Br J Vener Dis (1971) 4.17

On the use of sequence homologies to predict protein structure: identical pentapeptides can have completely different conformations. Proc Natl Acad Sci U S A (1984) 4.08

Equity in the delivery of health care in Europe and the US. J Health Econ (2000) 3.84

High-frequency mutagenesis of human cells and characterization of a mutant unresponsive to both alpha and gamma interferons. Proc Natl Acad Sci U S A (1991) 3.83

The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue. Nature (1995) 3.61

Crystal structures of myoglobin-ligand complexes at near-atomic resolution. Biophys J (1999) 3.55

Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway. Mol Cell Biol (1989) 3.49

Equity in the finance of health care: some further international comparisons. J Health Econ (1999) 3.48

Time-resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis. Nature (1990) 3.47

Structural proteomics of an archaeon. Nat Struct Biol (2000) 3.46

The ras protein family: evolutionary tree and role of conserved amino acids. Biochemistry (1991) 3.38

Treatment of gonorrhoea with single oral doses of ampicillin plus probenecid. I. Comparison with procaine penicillin. Br J Vener Dis (1973) 3.37

From micro- to nanofabrication with soft materials. Science (2000) 3.14

Interaction of the nuclear GTP-binding protein Ran with its regulatory proteins RCC1 and RanGAP1. Biochemistry (1995) 2.91

Expression of p21 proteins in Escherichia coli and stereochemistry of the nucleotide-binding site. EMBO J (1986) 2.85

Structure of the regulatory domain of scallop myosin at 2.8 A resolution. Nature (1994) 2.78

Substrate positions and induced-fit in crystalline adenylate kinase. J Mol Biol (1977) 2.69

GTPase-activating proteins: helping hands to complement an active site. Trends Biochem Sci (1998) 2.64

The bottleneck in AZT activation. Nat Med (1997) 2.61

Similarity of the three-dimensional structures of actin and the ATPase fragment of a 70-kDa heat shock cognate protein. Proc Natl Acad Sci U S A (1991) 2.61

Kinetics of interaction of nucleotides with nucleotide-free H-ras p21. Biochemistry (1990) 2.55

Structural and mechanistic insights into the interaction between Rho and mammalian Dia. Nature (2005) 2.52

Ras/Rap effector specificity determined by charge reversal. Nat Struct Biol (1996) 2.52

Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras. Nat Struct Biol (1997) 2.43

Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. J Biol Chem (2000) 2.42

The 1.7 A crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller. Nature (1998) 2.42

Structure of mitochondrial creatine kinase. Nature (1996) 2.33

Substrate-assisted catalysis as a mechanism for GTP hydrolysis of p21ras and other GTP-binding proteins. Nat Struct Biol (1995) 2.32

A comparison of batch effect removal methods for enhancement of prediction performance using MAQC-II microarray gene expression data. Pharmacogenomics J (2010) 2.30

Vacuum Rabi splitting with a single quantum dot in a photonic crystal nanocavity. Nature (2004) 2.28

Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Cell (2001) 2.28

Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc Natl Acad Sci U S A (2000) 2.28

Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins. Nature (2000) 2.25

Analysis of radiation-pressure induced mechanical oscillation of an optical microcavity. Phys Rev Lett (2005) 2.25

Kinetic and structural analysis of the Mg(2+)-binding site of the guanine nucleotide-binding protein p21H-ras. J Biol Chem (1993) 2.23

The kinetic mechanism of Ran--nucleotide exchange catalyzed by RCC1. Biochemistry (1995) 2.20

Electrostatic stress in catalysis: structure and mechanism of the enzyme orotidine monophosphate decarboxylase. Proc Natl Acad Sci U S A (2000) 2.18

Structural view of the Ran-Importin beta interaction at 2.3 A resolution. Cell (1999) 2.15

Differential interaction of the ras family GTP-binding proteins H-Ras, Rap1A, and R-Ras with the putative effector molecules Raf kinase and Ral-guanine nucleotide exchange factor. J Biol Chem (1996) 2.14

Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product. Science (1990) 2.09

Nosocomial infections due to Pseudomonas aeruginosa: review of recent trends. Rev Infect Dis (1984) 2.08

How good are predictions of protein secondary structure? FEBS Lett (1983) 2.08

Risk equalization, competition and choice in Germany: a reply to Wysong and Abel. Soz Praventivmed (1998) 2.05

The structure of Ras protein: a model for a universal molecular switch. Trends Biochem Sci (1991) 2.02

The ten helical twist angles of B-DNA. Nucleic Acids Res (1982) 2.02

Structure of the detoxification catalyst mercuric ion reductase from Bacillus sp. strain RC607. Nature (1991) 2.01

Dynamic properties of the Ras switch I region and its importance for binding to effectors. Proc Natl Acad Sci U S A (2001) 1.99

Kinetic analysis by fluorescence of the interaction between Ras and the catalytic domain of the guanine nucleotide exchange factor Cdc25Mm. Biochemistry (1998) 1.97

Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue: implications for nuclear transport. Nature (1999) 1.97

Structure of a ligand-binding intermediate in wild-type carbonmonoxy myoglobin. Nature (2000) 1.96

Quantitative analysis of the complex between p21ras and the Ras-binding domain of the human Raf-1 protein kinase. J Biol Chem (1995) 1.94

Mutational and kinetic analyses of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity. Mol Cell Biol (1992) 1.93

The structure of OmpF porin in a tetragonal crystal form. Structure (1995) 1.87

Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail. Proc Natl Acad Sci U S A (2001) 1.86

Biochemical properties of Ha-ras encoded p21 mutants and mechanism of the autophosphorylation reaction. J Biol Chem (1988) 1.85

Formation of a transition-state analog of the Ras GTPase reaction by Ras-GDP, tetrafluoroaluminate, and GTPase-activating proteins. Science (1996) 1.85

Structure of thymidylate kinase reveals the cause behind the limiting step in AZT activation. Nat Struct Biol (1997) 1.77

RNA1 encodes a GTPase-activating protein specific for Gsp1p, the Ran/TC4 homologue of Saccharomyces cerevisiae. J Biol Chem (1995) 1.77

A simplified procedure for the isolation of bacterial polypeptide elongation factor EF-Tu. Anal Biochem (1980) 1.74

Conformational transitions in p21ras and in its complexes with the effector protein Raf-RBD and the GTPase activating protein GAP. Biochemistry (1996) 1.69

A microfabricated device for sizing and sorting DNA molecules. Proc Natl Acad Sci U S A (1999) 1.67

Treatment of gonorrhoea with single oral doses of ampicillin plus probenecid. II. Comparison of results in London and Wales. Br J Vener Dis (1973) 1.65

The role of cavities in protein dynamics: crystal structure of a photolytic intermediate of a mutant myoglobin. Proc Natl Acad Sci U S A (2000) 1.63

Analysis of intrinsic and CDC25-stimulated guanine nucleotide exchange of p21ras-nucleotide complexes by fluorescence measurements. Methods Enzymol (1995) 1.63

The structure of the flavoenzyme glutathione reductase. Nature (1978) 1.61

Simplified method for the cultural diagnosis of gonorrhoea. Br J Vener Dis (1976) 1.58

Human monocyte CD14 is upregulated by lipopolysaccharide. Infect Immun (1996) 1.57

Three-dimensional structure of the complex of skeletal muscle actin and bovine pancreatic DNAse I at 6-A resolution. Proc Natl Acad Sci U S A (1981) 1.57

Structure and mechanism of the glycyl radical enzyme pyruvate formate-lyase. Nat Struct Biol (1999) 1.57

Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight. Nature (2012) 1.56

Cryptotomography: reconstructing 3D Fourier intensities from randomly oriented single-shot diffraction patterns. Phys Rev Lett (2010) 1.55