Abstract:
:DegP, a member of the highly conserved HtrA family of proteases, performs a regulated proteolysis of toxic misfolded proteins in the periplasm of Gram-negative bacteria. The allosteric switch between inactive and active conformations is a central mechanism to carefully control proteolytic activity of DegP and to maintain the optimal cellular fitness, but few other molecules than substrates are known to allosterically control DegP activity. Here, we demonstrate that a mutant variant of an outer-membrane lipoprotein, Lpp+Leu, can function as a novel allosteric effector that changes the dynamic range of DegP activity. The three leucines at the C-termini of trimeric Lpp+Leu are central components for activity modulation. Selection experiments with Lpp variant libraries show that Lpp variants with diverse sequences at or near C-termini, in particular those with hydrophobic residues at C-termini, function similarly to Lpp+Leu. Interestingly, Lpp variants carrying different residues at C-terminal, penultimate, or antepenultimate positions display dramatically different patterns of activation and inhibition effects, suggesting that their interactions with DegP differentially stabilize distinct inactive or active conformations. We propose that the tripodal structure with three hydrophobic ends that mimics Lpp+Leu is a novel platform for allosteric effectors, which may be useful in developing new antibiotics against DegP or homologous HtrA proteases.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Park H,Kim YT,Choi C,Kim Sdoi
10.1016/j.jmb.2017.09.011subject
Has Abstractpub_date
2017-10-13 00:00:00pages
3090-3101issue
20eissn
0022-2836issn
1089-8638pii
S0022-2836(17)30448-5journal_volume
429pub_type
杂志文章abstract::The family of fibroblast growth factor receptors (FGFRs) plays an important and well-characterized role in a variety of pathological disorders. FGFR4 is involved in myogenesis and muscle regeneration. Mutations affecting the kinase domain of FGFR4 may cause cancer, for example, breast cancer or rhabdomyosarcoma. Where...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2014.09.004
更新日期:2014-11-11 00:00:00
abstract::RNase MRP is a ribonucleoprotein endoribonuclease involved in eukaryotic pre-rRNA processing. The enzyme possesses a putatively catalytic RNA subunit, structurally related to that of RNase P. A thorough structure analysis of Saccharomyces cerevisiae MRP RNA, entailing enzymatic and chemical probing, mutagenesis and th...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.05.076
更新日期:2004-08-06 00:00:00
abstract::Integration host factor (IHF) of Escherichia coli is a histone-like protein that is involved both in site-specific recombination and in regulating the expression of a number of phage and bacterial genes. We have shown previously that transcription of the ilvGMEDA operon in E. coli is greatly reduced in IHF mutants. We...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(88)90212-4
更新日期:1988-10-05 00:00:00
abstract::The worm-like chain model has often been employed to describe the average conformation of long, intrinsically straight polymer molecules, including DNA. The present study extends the applicability of the worm-like chain model to polymers containing bends or sections of different flexibility. Several cases have been ex...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.1830
更新日期:1998-07-03 00:00:00
abstract::TolQ, TolR and TolA are membrane proteins involved in maintaining the structure of Escherichia coli cell envelope. TolQ and TolR span the inner membrane with three and with one alpha-helical segments, respectively. The tolQ925 mutation (A177V), located in the third putative transmembrane helix of TolQ (TolQ-III), indu...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.0058
更新日期:1995-02-10 00:00:00
abstract::Inositol 1,4,5-trisphosphate receptors in Caenorhabditis elegans are encoded by a single gene, itr-1. This provides a powerful system in which to dissect the mechanisms that control the tissue-specific expression of molecules that determine the specificity of calcium signalling. We first identified the Caenorhabditis ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.4388
更新日期:2001-02-16 00:00:00
abstract::The high mobility group (HMG) domain is a DNA binding motif found in some eukaryotic chromosomal proteins and transcription factors. This domain binds in the minor groove of DNA inducing a sharp bend and also preferentially binds to certain distorted DNA structures. Although structures of sequence-specific HMG domains...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.3246
更新日期:1999-11-19 00:00:00
abstract::The Src homology 3 (SH3) domain of pp60(c-src) (Src) plays dual roles in signal transduction, through stabilizing the repressed form of the Src kinase and through mediating the formation of activated signaling complexes. Transition of the Src SH3 domain between a variety of binding partners during progression through ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2001.5083
更新日期:2001-11-02 00:00:00
abstract::The Psi-RNA packaging signal of the human immunodeficiency virus type-1 (HIV-1) genome contains a 35 nucleotide stem-loop, termed SL1, which is important for efficient genome packaging during virus assembly and for reverse transcription during infectivity. The predicted secondary structure of SL1 consists of an upper ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(02)01305-0
更新日期:2003-02-14 00:00:00
abstract::The crystal structure of rubredoxin from the sulfate-reducing bacterium Desulfovibrio gigas has been determined at 1.4 A resolution (1 A = 0.1 nm) by X-ray diffraction methods; starting with a model of the isostructural rubredoxin from Desulfovibrio vulgaris. Refinement of the molecular model has been carried out by r...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(87)90562-6
更新日期:1987-10-05 00:00:00
abstract::The catalytic pentad of tyrosine recombinases, that assists the tyrosine nucleophile, includes a conserved histidine/tryptophan (His/Trp-III). Flp and Cre harbor tryptophan at this position; most of their kin recombinases display histidine. Contrary to the conservation rule, Flp(W330F) is a much stronger recombinase t...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.02.022
更新日期:2007-04-20 00:00:00
abstract::FGF21 is a member of a unique subfamily of fibroblast growth factors that function as endocrine hormones and regulate a variety of metabolic activities. Unlike paracrine FGFs, FGF21 does not bind heparin and requires βKlotho as a co-receptor to activate FGFR signaling. In the presence of βKlotho, FGF21 is able to acti...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2011.03.003
更新日期:2011-05-06 00:00:00
abstract::The nucleic acid content of enriched preparations of mitochondria/tubulofilamentous particles from normal and scrapie-infected hamster brains were examined by electron microscopy. After spreading on collodion-coated grids circular molecules of approximately 15.7 kb corresponding in size to mitochondrial DNA (mtDNA) we...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(90)90369-W
更新日期:1990-12-05 00:00:00
abstract::We used transient phosphorescence anisotropy to detect the microsecond rotational dynamics of erythrosin-iodoacetamide-labeled actin strongly bound to single-headed fragments of muscle myosin subfragment 1 (S1) and non-muscle myosin V (MV). The conformational dynamics of actin filaments in solution are markedly influe...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.11.063
更新日期:2010-02-26 00:00:00
abstract::The Ser/Thr kinase CK2 (former name: casein kinase 2) is a heterotetrameric enzyme composed of two catalytic chains (CK2alpha) attached to a dimer of noncatalytic subunits. Together with the cyclin-dependent kinases and the mitogen-activated protein kinases, CK2alpha belongs to the CMGC family of the eukaryotic protei...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.01.008
更新日期:2008-03-14 00:00:00
abstract::Historically referred to as "the GTPase center", the L11 binding region (L11BR) of Escherichia coli 23 S rRNA is a highly conserved structure that has been implicated in several essential functions during protein synthesis. Here, in vivo expression of an RNA fragment containing that structure was found to affect trans...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/S0022-2836(02)00304-2
更新日期:2002-05-31 00:00:00
abstract::Toxoplasma gondii is a ubiquitous parasitic protozoan causing congenital infection and severe encephalitis in the course of the acquired immunodeficiency syndrome. Glycosyl-phosphatidylinositols of T. gondii have been shown to be identical with the low molecular weight antigen which elicits an early immunoglobulin M i...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0806
更新日期:1997-03-07 00:00:00
abstract::Serine 31 of histone H3.3 is phosphorylated during mitosis in mammalian cells and has been shown to influence chromosome segregation. We established a screening system to identify candidate kinase(s) phosphorylating H3.3S31 by using siRNA library targeting 720 human kinases, and we confirmed the results with an indepe...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2017.01.016
更新日期:2017-06-30 00:00:00
abstract::Type IV pili are multifunctional filaments displayed on many bacterial pathogens. Members of the Type IVa pilus subclass are found on a diverse group of human pathogens, whereas Type IVb pili are found almost exclusively on enteric bacteria. The Type IVa and IVb subclasses are distinguished by differences in the pilin...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2012.02.017
更新日期:2012-04-20 00:00:00
abstract::The interactions between the complement receptor type 2 (CR2) and the C3 complement fragments C3d, C3dg, and iC3b are essential for the initiation of a normal immune response. A crystal-derived structure of the two N-terminal short consensus repeat (SCR1-2) domains of CR2 in complex with C3d has previously been elucid...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.10.005
更新日期:2010-12-10 00:00:00
abstract::In the prokaryotic homolog of the eukaryotic proteasome, HslUV, the "double donut" HslV protease is allosterically activated by HslU, an AAA protein of the Clp/Hsp100 family consisting of three (amino-terminal, carboxy-terminal, and intermediate) domains. The intermediate domains of HslU, which extend like tentacles f...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00580-1
更新日期:2003-07-04 00:00:00
abstract::We have established a time-resolved fluorescence assay to study fibrillation of the 29 residue peptide hormone glucagon under a variety of different conditions in a high-throughput format. Fibrils formed at pH 2.5 differ in fibrillation kinetics, morphology, thioflavin T staining and FTIR/CD spectra depending on salts...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.09.100
更新日期:2006-01-20 00:00:00
abstract::Natriuretic peptides are cyclic vasoactive peptide hormones with great diagnostic and therapeutic relevance. The main catabolic pathway postulated for natriuretic peptides is the degradation by neutral endopeptidase (NEP). However, B-type natriuretic peptide has been found to be resistant to NEP. Here, we compared the...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.08.025
更新日期:2009-10-23 00:00:00
abstract::A mutant version of the N-terminal domain of Escherichia coli DnaB helicase was used as a model system to assess the stabilization against unfolding gained by covalent cyclization. Cyclization was achieved in vivo by formation of an amide bond between the N and C termini with the help of a split mini-intein. Linear an...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.12.037
更新日期:2005-03-04 00:00:00
abstract::The intracellular ileal lipid binding proteins (ILBPs) are involved in the transport and enterohepatic circulation of bile acids. ILBPs from different species show high sequence and structural homology and have been shown to bind multiple bile acid ligands with differing degrees of selectivity and positive co-operativ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.06.024
更新日期:2007-08-31 00:00:00
abstract::The soluble domain of the self-assembly vaccinia virus envelope protein A27L, sA27L-aa, consists of a flexible extended coil at the N terminus and a rigid hydrophobic coiled-coil region at the C terminus. In the former, a basic strip of 12 residues is responsible for binding to cell-surface heparan sulfates. Although ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.04.024
更新日期:2005-06-24 00:00:00
abstract::Opsins are widespread photoreceptor proteins involved in a diversity of light-driven processes in all major taxa that use the apocarotenoid retinal as a light-absorbing prosthetic group. Proteins from the opsin family are also found in filamentous fungi, but no function has been attributed to them. The fungus Fusarium...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.01.057
更新日期:2009-03-20 00:00:00
abstract::The Mycobacterium leprae RuvA homologue (MlRuvA) was over-expressed in Escherichia coli and purified to homogeneity. The DNA-binding specificity and the functional interactions of MlRuvA with E. coli RuvB and RuvC (EcRuvB and EcRuvC) were examined using synthetic Holliday junctions. MlRuvA bound specifically to Hollid...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.4009
更新日期:2000-08-25 00:00:00
abstract::The promoter and operator sequences of the Tn10-encoded tetracycline resistance operon are determined in vitro by transcription studies of purified DNA restriction fragments, protection of guanosine from methylation by dimethylsulphate, and DNase I footprinting employing the purified TET repressor protein. In vitro tr...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(84)80037-6
更新日期:1984-01-15 00:00:00
abstract::The pathway for oxidative degradation of nicotine in Arthrobacter nicotinovorans includes two genetically and structurally unrelated flavoenzymes, 6-hydroxy-L-nicotine oxidase (6HLNO) and 6-hydroxy-D-nicotine oxidase, which act with absolute stereospecificity on the L- and D-forms, respectively, of 6-hydroxy-nicotine....
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.12.009
更新日期:2010-02-26 00:00:00