当前位置： SCI文献检索 > JOURNAL OF MOLECULAR BIOLOGY期刊下所有文献 > Noncompetitive inhibition of hepatocyte growth factor-dependent Met signaling by a phage-derived peptide.

Noncompetitive inhibition of hepatocyte growth factor-dependent Met signaling by a phage-derived peptide.

Abstract：

:Dysregulation of hepatocyte growth factor (HGF)-induced signaling via its receptor tyrosine kinase Met results in tumor progression and metastasis. To initiate signaling, pro-HGF must be proteolytically activated to reveal a secondary Met binding site within the serine protease-like beta-chain of HGF. Although HGF/Met is a large complex, we sought to discover relatively small antagonists that might interfere with this critical Met binding region. Pools of disulfide-constrained random peptide libraries displayed on phage were selected for binding to HGF, ultimately resulting in a disulfide-constrained 15-mer peptide (VNWVCFRDVGCDWVL) termed HB10, which bound to the recombinant human HGF beta-chain (HGF beta) and competitively inhibited binding to Met with an IC(50) of 450 nM. In MDA-MB435 cells, HB10 reduced HGF-dependent Met phosphorylation by 70%, and phosphorylation of downstream kinases AKT and ERK1/ERK2 by 74% and 69%, respectively. Addition of HB10 also inhibited HGF-dependent migration of these cells with an IC(50) of approximately 20 microM. The 2D (1)H-NMR structure of HB10 revealed a beta-hairpin loop stabilized by the disulfide bond and cross-strand pairing of Trp3 and Trp13. HGF beta mutants deficient in Met binding also have reduced HB10 binding, suggesting an overlapping binding site. Notably HB10 did not inhibit full length HGF binding to Met. Thus steric hindrance of the interaction between HGF beta domain binding to Met is sufficient for inhibiting full-length HGF-dependent Met signaling and cell migration that is consistent with a noncompetitive inhibitory mechanism of Met signal transduction.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Tam EM,Runyon ST,Santell L,Quan C,Yao X,Kirchhofer D,Skelton NJ,Lazarus RA

doi

10.1016/j.jmb.2008.09.091

subject

Has Abstract

pub_date

2009-01-09 00:00:00

pages

79-90

issue

1

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(08)01293-X

journal_volume

385

pub_type

杂志文章

相关文献

JOURNAL OF MOLECULAR BIOLOGY文献大全
  • Nucleotide-dependent lateral and longitudinal interactions in microtubules.

    abstract：:Microtubule (MT) stability is related to the hydrolysis of the guanosine triphosphate nucleotide (NT) bound to β-tubulin. However, the molecular mechanism by which the NT state influences the stability of the contacts in the MT lattice remains elusive. Here, we present large-scale atomistic simulations of different tu...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2013.03.029

    authors： Grafmüller A,Noya EG,Voth GA

    更新日期：2013-06-26 00:00:00

  • The mechanism of loading of the FLP recombinase onto its DNA target sequence.

    abstract：:The FLP recombinase interacts with its target sequence with the formation of three distinct DNA-protein complexes. The first complex leaves neither a DNase footprint nor is the DNA protected from methylation by dimethyl sulfate. We have found, however, that the FLP protein is bound predominantly to only one of the thr...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(88)90576-1

    authors： Beatty LG,Sadowski PD

    更新日期：1988-11-20 00:00:00

  • Specific heteromeric association of four transmembrane peptides derived from platelet glycoprotein Ib-IX complex.

    abstract：:As the receptor on the platelet surface for von Willebrand factor, glycoprotein (GP) Ib-IX complex is critically involved in hemostasis and thrombosis. How the complex is assembled from GP Ibalpha, GP Ib beta and GP IX subunits, all of which are type I transmembrane proteins, is not entirely clear. Genetic and mutatio...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.07.037

    authors： Luo SZ,Li R

    更新日期：2008-10-03 00:00:00

  • The crystal structure of affinity-matured human growth hormone at 2 A resolution.

    abstract：:A variant of human growth hormone (hGH), in which 15 mutations were introduced with phage display mutagenesis to improve receptor binding affinity by 400-fold, yielded two related crystal forms diffracting to high resolution. The structure of this variant was determined in both crystal forms, one at 2.0 A resolution a...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1994.1135

    authors： Ultsch MH,Somers W,Kossiakoff AA,de Vos AM

    更新日期：1994-02-11 00:00:00

  • An amphipathic alpha-helix at a membrane interface: a structural study using a novel X-ray diffraction method.

    abstract：:The amphipathic alpha-helix is a recurrent feature of membrane-active proteins, peptides, and toxins. Despite extensive biophysical studies, the structural details of its affinity for membrane interfaces remain rather vague. We report here the first results of an effort to obtain detailed structural information about ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1999.2840

    authors： Hristova K,Wimley WC,Mishra VK,Anantharamiah GM,Segrest JP,White SH

    更新日期：1999-07-02 00:00:00

  • Crystallization and preliminary X-ray analysis of Gc, the vitamin D-binding protein in serum.

    abstract：:The vitamin D-binding protein, Gc, was purified from human serum and crystallized using the hanging-drop method. The best crystals were grown from 28% polyethylene glycol 400 in 50 mM-sodium acetate at pH 4.8. These crystals diffract to 3.4 A and the observed diffraction is consistent with orthorhombic space groups P4...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(91)90097-p

    authors： Vogelaar NJ,Lindberg U,Schutt CE

    更新日期：1991-08-05 00:00:00

  • Modulation of K11-linkage formation by variable loop residues within UbcH5A.

    abstract：:Ubiquitination refers to the covalent addition of ubiquitin (Ub) to substrate proteins or other Ub molecules via the sequential action of three enzymes (E1, E2, and E3). Recent advances in mass spectrometry proteomics have made it possible to identify and quantify Ub linkages in biochemical and cellular systems. We us...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2011.03.011

    authors： Bosanac I,Phu L,Pan B,Zilberleyb I,Maurer B,Dixit VM,Hymowitz SG,Kirkpatrick DS

    更新日期：2011-05-06 00:00:00

  • Nucleotide sequences of immunoglobulin-epsilon pseudogenes in man and apes and their phylogenetic relationships.

    abstract：:To understand the phylogenetic relationships between hominoids, the nucleotide sequences of immunoglobulin-epsilon processed pseudogenes from chimpanzee, gorilla and orangutan were determined. The basic structures of these processed pseudogenes agreed with their human counterpart. Although the degrees of nucleotide di...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(89)90366-5

    authors： Ueda S,Watanabe Y,Saitou N,Omoto K,Hayashida H,Miyata T,Hisajima H,Honjo T

    更新日期：1989-01-05 00:00:00

  • Evolved Lactococcus lactis strains for enhanced expression of recombinant membrane proteins.

    abstract：:The production of complex multidomain (membrane) proteins is a major hurdle in structural genomics and a generic approach for optimizing membrane protein expression is still lacking. We have devised a selection method to isolate mutant strains with improved functional expression of recombinant membrane proteins. By fu...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2010.06.002

    authors： Linares DM,Geertsma ER,Poolman B

    更新日期：2010-08-06 00:00:00

  • Protein Interaction Energy Landscapes are Shaped by Functional and also Non-functional Partners.

    abstract：:In the crowded cell, a strong selective pressure operates on the proteome to limit the competition between functional and non-functional protein-protein interactions. We developed an original theoretical framework in order to interrogate how this competition constrains the behavior of proteins with respect to their pa...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2019.12.047

    authors： Schweke H,Mucchielli MH,Sacquin-Mora S,Bei W,Lopes A

    更新日期：2020-02-14 00:00:00

  • A critical assessment of putative gatekeeper interactions in the villin headpiece helical subdomain.

    abstract：:The helical subdomain of the villin headpiece (HP36) is one of the smallest naturally occurring proteins that folds cooperatively. Its small size, rapid folding, and simple three-helix topology have made it an extraordinary popular model system for computational, theoretical, and experimental studies of protein foldin...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2010.05.070

    authors： Xiao S,Raleigh DP

    更新日期：2010-08-13 00:00:00

  • Peptide models of local and long-range interactions in the molten globule state of human alpha-lactalbumin.

    abstract：:alpha-Lactalbumin, a small calcium-binding protein, forms an equilibrium molten globule state under a variety of conditions. A set of four peptides designed to probe the role of local interactions and the role of potential long-range interactions in stabilizing the molten globule of alpha-lactalbumin has been prepared...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1998.2099

    authors： Demarest SJ,Fairman R,Raleigh DP

    更新日期：1998-01-01 00:00:00

  • Probing a tRNA core that contributes to aminoacylation.

    abstract：:The contribution of the tRNA "core" to aminoacylation is beginning to be recognized. One example is the core region of Escherichia coli tRNA(Cys), which has been shown by biochemical studies to be important for aminoacylation. This core has several layers of unusual base-pairs, which are revealed by the recent crystal...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1999.3353

    authors： Hamann CS,Hou YM

    更新日期：2000-01-28 00:00:00

  • The SH3 domain of nebulin binds selectively to type II peptides: theoretical prediction and experimental validation.

    abstract：:Nebulin, a giant modular protein from muscle, is thought to act as a molecular ruler in sarcomere assembly. The C terminus of nebulin, located in the sarcomere Z-disk, comprises an SH3 domain, a module well known for its role in protein/protein interactions. SH3 domains are known to recognize proline-rich ligands, whi...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2001.5312

    authors： Politou AS,Spadaccini R,Joseph C,Brannetti B,Guerrini R,Helmer-Citterich M,Salvadori S,Temussi PA,Pastore A

    更新日期：2002-02-15 00:00:00

  • Structure of selenophosphate synthetase essential for selenium incorporation into proteins and RNAs.

    abstract：:Selenophosphate synthetase (SPS) catalyzes the activation of selenide with adenosine 5'-triphosphate (ATP) to generate selenophosphate, the essential reactive selenium donor for the formation of selenocysteine (Sec) and 2-selenouridine residues in proteins and RNAs, respectively. Many SPS are themselves Sec-containing...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.08.042

    authors： Itoh Y,Sekine S,Matsumoto E,Akasaka R,Takemoto C,Shirouzu M,Yokoyama S

    更新日期：2009-02-06 00:00:00

  • A distal, high-affinity binding site on the cyclin-CDK substrate Pho4 is important for its phosphorylation and regulation.

    abstract：:Cyclins and cyclin-dependent kinases (CDKs) are key components of signaling pathways essential for cell growth and survival. The cyclin-CDK Pho80-Pho85 inactivates the transcription factor Pho4 in budding yeast by phosphorylating it on five sites. We isolated seven single amino acid substitutions outside of the phosph...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2003.10.035

    authors： Byrne M,Miller N,Springer M,O'Shea EK

    更新日期：2004-01-02 00:00:00

  • Structure of the ligand-blocked periplasmic entrance of the bacterial multidrug efflux protein TolC.

    abstract：:The trimeric TolC protein of Escherichia coli comprises an outer membrane beta-barrel and a contiguous alpha-helical barrel projecting across the periplasm. This provides a single 140 A long pore for multidrug efflux and protein export. We have previously reported that trivalent cations such as hexammine cobalt can se...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2004.07.088

    authors： Higgins MK,Eswaran J,Edwards P,Schertler GF,Hughes C,Koronakis V

    更新日期：2004-09-17 00:00:00

  • Order of steps in the cytochrome C folding pathway: evidence for a sequential stabilization mechanism.

    abstract：:Previous work used hydrogen exchange (HX) experiments in kinetic and equilibrium modes to study the reversible unfolding and refolding of cytochrome c (Cyt c) under native conditions. Accumulated results now show that Cyt c is composed of five individually cooperative folding units, called foldons, which unfold and re...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2006.04.035

    authors： Krishna MM,Maity H,Rumbley JN,Lin Y,Englander SW

    更新日期：2006-06-23 00:00:00

  • NMR structure of the integral membrane protein OmpX.

    abstract：:The structure of the integral membrane protein OmpX from Escherichia coli reconstituted in 60 kDa DHPC micelles (OmpX/DHPC) was calculated from 526 NOE upper limit distance constraints. The structure determination was based on complete sequence-specific assignments for the amide protons and the Val, Leu, and Ile(delta...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2003.09.014

    authors： Fernández C,Hilty C,Wider G,Güntert P,Wüthrich K

    更新日期：2004-03-05 00:00:00

  • The three-dimensional structure at 2.4 A resolution of glycosylated proteinase A from the lysosome-like vacuole of Saccharomyces cerevisiae.

    abstract：:The crystal structures of glycosylated native proteinase A, an aspartic proteinase found in the vacuole of Saccharomyces cerevisiae, and its complex with a difluorostatone-containing tripeptide have been determined by molecular replacement to 3.5 A and 2.4 A resolutions, respectively. Superposition of the bound and na...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1996.0880

    authors： Aguilar CF,Cronin NB,Badasso M,Dreyer T,Newman MP,Cooper JB,Hoover DJ,Wood SP,Johnson MS,Blundell TL

    更新日期：1997-04-11 00:00:00

  • Mutant p53 in Cancer: Accumulation, Gain-of-Function, and Therapy.

    abstract：:Tumor suppressor p53 plays a central role in tumor suppression. p53 is the most frequently mutated gene in human cancer, and over half of human cancers contain p53 mutations. Majority of p53 mutations in cancer are missense mutations, leading to the expression of full-length mutant p53 (mutp53) protein. While the crit...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章,评审

    doi：10.1016/j.jmb.2017.03.030

    authors： Yue X,Zhao Y,Xu Y,Zheng M,Feng Z,Hu W

    更新日期：2017-06-02 00:00:00

  • NMR structure of the HIV-1 regulatory protein VPR.

    abstract：:The human immunodeficiency virus type 1 (HIV-1) genome encodes a highly conserved regulatory gene product, Vpr (96 residues, 14kDa), which is incorporated into virions. In the infected cells, Vpr, expressed late in the virus cycle, is believed to function in the early phases of HIV-1 replication, such as nuclear migra...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(03)00060-3

    authors： Morellet N,Bouaziz S,Petitjean P,Roques BP

    更新日期：2003-03-14 00:00:00

  • Interactions between morpholinyl anthracyclines and DNA. The crystal structure of a morpholino doxorubicin bound to d(CGTACG).

    abstract：:Anthracycline antibiotics daunomycin and adriamycin are among the most widely used in cancer chemotherapy and DNA is believed to be the primary target of their biological action. The crystal structure of a morpholino derivative of adriamycin bound to the DNA hexamer d(CGTACG) has been determined at 1.5 A resolution. T...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1993.1208

    authors： Cirilli M,Bachechi F,Ughetto G,Colonna FP,Capobianco ML

    更新日期：1993-04-05 00:00:00

  • Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses.

    abstract：:A detailed phylogenetic analysis for mammalian members of the family Herpesviridae, based on molecular sequences is reported. Sets of encoded amino acid sequences were collected for eight well conserved genes that are common to mammalian herpesviruses. Phylogenetic trees were inferred from alignments of these sequence...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1995.0152

    authors： McGeoch DJ,Cook S,Dolan A,Jamieson FE,Telford EA

    更新日期：1995-03-31 00:00:00

  • Comparison of the refined crystal structures of liganded and unliganded chicken, yeast and trypanosomal triosephosphate isomerase.

    abstract：:The refined crystal structures of chicken, yeast and trypanosomal triosephosphate isomerase (TIM) have been compared. TIM is known to exist in an "open" (unliganded) and "closed" (liganded) conformation. For chicken TIM only the refined open structure is available, whereas for yeast TIM and trypanosomal TIM refined st...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(92)90473-w

    authors： Wierenga RK,Noble ME,Davenport RC

    更新日期：1992-04-20 00:00:00

  • Crystallization and preliminary X-ray analysis of gamma-glutamyltranspeptidase from Escherichia coli K-12.

    abstract：:gamma-Glutamyltranspeptidase (EC 2.3.2.2) from Escherichia coli K-12 has been purified and crystallized by means of vapor diffusion in hanging drops. Two kinds of crystals on cell dimensions were found for X-ray diffraction analysis, one from ammonium sulfate and the other from polyethylene glycol 6000 as precipitants...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1993.1677

    authors： Kumagai H,Nohara S,Suzuki H,Hashimoto W,Yamamoto K,Sakai H,Sakabe K,Fukuyama K,Sakabe N

    更新日期：1993-12-20 00:00:00

  • Common physical properties of DNA affecting target site selection of sleeping beauty and other Tc1/mariner transposable elements.

    abstract：:Sleeping Beauty (SB) is the most active Tc1/mariner-type transposable element in vertebrates, and is therefore a valuable vector for transposon mutagenesis in vertebrate models and for human gene therapy. We have analyzed factors affecting target site selection of SB in mammalian cells, by generating transposition eve...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(02)00991-9

    authors： Vigdal TJ,Kaufman CD,Izsvák Z,Voytas DF,Ivics Z

    更新日期：2002-10-25 00:00:00

  • Structure of a Ca(2+)/CaM:Kv7.4 (KCNQ4) B-helix complex provides insight into M current modulation.

    abstract：:Calmodulin (CaM) is an important regulator of Kv7.x (KCNQx) voltage-gated potassium channels. Channels from this family produce neuronal M currents and cardiac and auditory I(KS) currents and harbor mutations that cause arrhythmias, epilepsy, and deafness. Despite extensive functional characterization, biochemical and...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2012.11.023

    authors： Xu Q,Chang A,Tolia A,Minor DL Jr

    更新日期：2013-01-23 00:00:00

  • High-resolution structural analysis of mammalian profilin 2a complex formation with two physiological ligands: the formin homology 1 domain of mDia1 and the proline-rich domain of VASP.

    abstract：:Profilins are small proteins capable of binding actin, poly-l-proline and other proline-rich sequences, and phosphatidylinositol (4,5)-bisphosphate. A number of proline-rich ligands for profilin have been characterised, including proteins of the Ena/VASP and formin families. We have determined the high-resolution crys...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2007.10.050

    authors： Kursula P,Kursula I,Massimi M,Song YH,Downer J,Stanley WA,Witke W,Wilmanns M

    更新日期：2008-01-04 00:00:00

  • A New Type of Circular RNA derived from Nonconventional Introns in Nuclear Genes of Euglenids.

    abstract：:Nuclear protein-coding genes of euglenids (Discoba, Euglenozoa, Euglenida) contain conventional (spliceosomal) and nonconventional introns. The latter have been found only in euglenozoans. A unique feature of nonconventional introns is the ability to form a stable and slightly conserved RNA secondary structure bringin...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2020.166758

    authors： Gumińska N,Zakryś B,Milanowski R

    更新日期：2021-02-05 00:00:00