Abstract:
:Protein allostery plays a pivotal role in many regulatory processes. Prominent examples are cell-surface receptors, which allosterically transmit ligand-generated signals to their cytoplasmic domains, or bacterial transcription factors, which alternate between a free conformation and a DNA-bound conformation in response to binding an effector molecule. The bacterial transcription factor Tet repressor (TetR) belongs to the latter category and is regarded as highly adapted to tetracyclines (tc's) as effectors. However, peptides isolated in this study were able to trigger distinct allosteric behavior including induction, anti-induction and corepression. Binding of the peptides' C-terminal residues consistently occurs within the tc-binding pocket of TetR. However, an extensive analysis of TetR mutants revealed that inducing and anti-inducing peptides utilize different parts of the binding pocket to elicit their respective regulatory responses. This study demonstrates that even for transcription factors evolved for high effector specificity, alternative molecular structures can exert similar and even novel effects, provided that sufficient chemical diversity and molecular flexibility, as found in peptide libraries, is accompanied by an efficient in vivo selection system. The high number of bioactive peptides and their extensive sequence diversity suggests that switching from small-molecule-controlled transcription regulation to a signal transduction network might be rather easily accomplished. These findings will strongly affect protein-mediated regulation of gene expression.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Goeke D,Kaspar D,Stoeckle C,Grubmüller S,Berens C,Klotzsche M,Hillen Wdoi
10.1016/j.jmb.2011.12.009subject
Has Abstractpub_date
2012-02-10 00:00:00pages
33-45issue
1eissn
0022-2836issn
1089-8638pii
S0022-2836(11)01298-8journal_volume
416pub_type
杂志文章abstract::Binding of the TATA-binding protein (TBP) to the "TATA" sequences present in the promoters of eukaryotic class II genes is the first step in the sequential assembly of transcription pre-initiation complexes. Myriad structural changes, including severe bending of the DNA, accompany TBP-TATA complex formation. A detaile...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.2835
更新日期:1999-06-25 00:00:00
abstract::When influenza A virus infects host cells, its integral matrix protein M2 forms a proton-selective channel in the viral envelope. Although X-ray crystallography and NMR studies using fragment peptides have suggested that M2 stably forms a tetrameric channel irrespective of pH, the oligomeric states of the full-length ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2014.05.002
更新日期:2014-07-15 00:00:00
abstract::The crystal structure of desulforedoxin from Desulfovibrio gigas, a new homo-dimeric (2 x 36 amino acids) non-heme iron protein, has been solved by the SIRAS method using the indium-substituted protein as the single derivative. The structure was refined to a crystallographic R-factor of 16.9% at 1.8 A resolution. Nati...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1995.0465
更新日期:1995-09-01 00:00:00
abstract::RepA protein, encoded in the Pseudomonas pPS10 replicon, is a stable dimer in solution (dRepA), acting as a self-repressor of repA transcription through binding to an inverted repeat operator. However, RepA monomers (mRepA) are required to initiate plasmid replication upon binding to four directly repeated DNA sequenc...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.09.013
更新日期:2006-12-15 00:00:00
abstract::Here, we have investigated the specificity of purified recombinant tRNA:m(2)(2)G10 methyltransferase of Pyrococcus abyssi ((Pab)Trm-m(2)(2)G10 enzyme). This archaeal enzyme catalyses mono- and dimethylation of the N(2)-exocyclic amino group of guanine at position 10 of several tRNA species. Our results indicate that o...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.12.087
更新日期:2006-03-24 00:00:00
abstract::ThiI is an enzyme responsible for the formation of the modified base S(4)U (4-thiouridine) found at position 8 in some prokaryotic tRNAs. This base acts as a sensitive trigger for the response mechanism to UV exposure, providing protection against its damaging effects. We present the crystal structure of Bacillus anth...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.11.013
更新日期:2006-02-10 00:00:00
abstract::Cytoplasmic polyadenylation element binding protein (CPEB) provides temporal and spatial control of protein synthesis required for early development and neuronal synaptic plasticity. CPEB regulates protein expression by inhibiting polyadenylation of selected mRNA transcripts, which prevents binding of the ribosome for...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2013.03.009
更新日期:2013-06-12 00:00:00
abstract::The recombination directionality factor, Xis, is a DNA bending protein that determines the outcome of integrase-mediated site-specific recombination by redesign of higher-order protein-DNA architectures. Although the attachment site DNA of mycobacteriophage Pukovnik is likely to contain four sites for Xis binding, Xis...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2013.10.002
更新日期:2014-01-23 00:00:00
abstract::Enoyl-[acyl carrier protein] (ACP) reductase (ENR) is a key enzyme in type II fatty acid synthesis that catalyzes the last step in each elongation cycle. Therefore, it has been considered as a target for antibiotics. However, recent studies indicate that some pathogens have more than one ENR; in particular, Bacillus s...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.12.003
更新日期:2011-02-25 00:00:00
abstract::Detailed atomic models of a eubacterial 5 S rRNA (spinach chloroplast 5 S rRNA) and of a eukaryotic 5 S rRNA (somatic and oocyte 5 S rRNA from Xenopus laevis) were built using computer graphic. Both models integrate stereochemical constraints and experimental data on the accessibility of bases and phosphates towards s...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(89)90264-7
更新日期:1989-05-20 00:00:00
abstract::Proteins with ultra-fast folding/unfolding kinetics are excellent candidates for study by molecular dynamics. Here, we describe such simulations of a three helix bundle protein, the engrailed homeodomain (En-HD), which folds via the diffusion-collision model. The unfolding pathway of En-HD was characterized by seven s...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.06.074
更新日期:2004-08-20 00:00:00
abstract::Only a few transcriptional regulatory proteins have been characterized in extremely hyperthermophilic organisms, and most function as repressors. Structural features of the NtrC1 protein from the hyperthermophilic bacterium Aquifex aeolicus suggested that this protein functions similarly to the sigma(54)-polymerase ac...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.08.003
更新日期:2005-10-21 00:00:00
abstract::The plasma of the striped bass Morone saxatilis contains a fucose-specific lectin (MsaFBP32) that consists of two F-type carbohydrate recognition domains (CRDs) in tandem. The crystal structure of the complex of MsaFBP32 with l-fucose reported here shows a cylindrical 81-A-long and 60-A-wide trimer divided into two gl...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.06.018
更新日期:2010-08-13 00:00:00
abstract::The extracellular matrix is a dynamic environment that constantly undergoes remodelling and degradation during vital physiological processes such as angiogenesis, wound healing, and development. Unbalanced extracellular matrix breakdown is associated with many diseases such as arthritis, cancer and fibrosis. Interstit...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.06.079
更新日期:2006-09-08 00:00:00
abstract::The Gram-negative organism Campylobacter jejuni is the major cause of food poisoning. Unlike Escherichia coli, which has two major porins, OmpC and OmpF, C. jejuni has one, termed major outer membrane protein (MOMP) through which nutrients and antibiotics transit. We report the 2.1-Å crystal structure of C. jejuni MOM...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2016.09.021
更新日期:2016-11-06 00:00:00
abstract::Long-standing questions on how peptides fold are addressed by the simulation at different temperatures of the reversible folding of a peptide in solution in atomic detail. Molecular dynamics simulations correctly predict the structure that is thermodynamically stable at 298 K, irrespective of the initial peptide confo...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.1885
更新日期:1998-07-31 00:00:00
abstract::The bacterial protein Rho triggers transcription termination at the ends of many operons and when transcription and translation become uncoupled. In addition to these genome wide activities, Rho implements regulation of specific genes by dictating whether RNA polymerase terminates transcription within the 5' leader re...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2015.10.020
更新日期:2015-12-04 00:00:00
abstract::G protein coupled receptors (GPCRs) are integral membrane proteins that mediate cellular responses to a wide variety of extracellular signals. However, the structural basis for activation of this class of receptors by ligand binding is not well understood. We report here the use of a systematic genetic protocol for id...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0816
更新日期:1997-02-28 00:00:00
abstract::The structure of the Escherichia coli gene coding for the metabolically stable 4.5 S RNA has been determined by cloning and DNA sequence analysis. Results from Southern hybridization assays carried out prior to cloning show the 4.5 S DNA to be limited to a single locus in the E. coli K12 genome. A 5.4 X 10(3) base DNA...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(84)90236-5
更新日期:1984-09-25 00:00:00
abstract::A protein microarray system containing different dilutions of 77 related and non-related proteins was used to show that IgE from subjects allergic to Brazil nut specifically recognise the seed 2S albumin protein (Ber e 1). Further, correctly folded chimaeric 2S albumin proteins containing structural epitope replacemen...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.08.065
更新日期:2004-10-22 00:00:00
abstract::The actin cytoskeleton is a complex network controlled by a vast array of intricately regulated actin-binding proteins. Human plastins (PLS1, PLS2, and PLS3) are evolutionary conserved proteins that non-covalently crosslink actin filaments into tight bundles. Through stabilization of such bundles, plastins contribute,...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2017.06.021
更新日期:2017-08-04 00:00:00
abstract::To search for submolecular foldon units, the spontaneous reversible unfolding and refolding of staphylococcal nuclease under native conditions was studied by a kinetic native-state hydrogen exchange (HX) method. As for other proteins, it appears that staphylococcal nuclease is designed as an assembly of well-integrate...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.12.020
更新日期:2008-02-29 00:00:00
abstract::Dipicolinic acid (DPA) is a small polar molecule that accumulates to high concentrations in bacterial endospores, and is thought to play a role in spore heat resistance, or the maintenance of heat resistance. Previous work has shown that mutations in the spoVF locus of Bacillus subtilis prevent the formation of DPA, a...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1993.1403
更新日期:1993-07-20 00:00:00
abstract::Human platelet profilin was expressed in Escherichia coli using a T7 based expression vector. The recombinant material is similar to authentic human platelet profilin based on the measured Kd for rabbit skeletal muscle actin. Crystals of the recombinant material were obtained from both PEG 8000 and (NH4)2SO4. These cr...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.1522
更新日期:1994-08-19 00:00:00
abstract::Bacteriophage with double-stranded, linear DNA genomes package DNA into pre-assembled icosahedral procapsids through a unique vertex. The packaging vertex contains an oligomeric ring of a portal protein that serves as a recognition site for the packaging enzymes, a conduit for DNA translocation, and the site of tail a...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2001.5275
更新日期:2002-02-01 00:00:00
abstract::The structure of recombinant human interleukin-4 (hIL-4) has been determined by both NMR and X-ray diffraction methods in several laboratories, including ours. The X-ray and NMR structures were successfully applied for solving the X-ray crystal structure by molecular replacement. Due to the small size of the hIL-4 mol...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.0144
更新日期:1995-03-24 00:00:00
abstract::We have used fluorescence resonance energy transfer to investigate the conformation of the apo and calcium-loaded states of the regulatory N-terminal domain of full-length troponin C mutants from skeletal muscle. The mutants studied each contained a single tryptophan residue (position 22 or 90) and a single cysteine r...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.1933
更新日期:1998-08-21 00:00:00
abstract::In a few, rather rare cases, frameshift mutant alleles are phenotypically suppressed during limitation for particular aminoacyl-tRNA species. The simplest interpretation is compensatory ribosome frameshifting at a "hungry" codon in the vicinity of the suppressed frameshift mutation. We have now tested this interpretat...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(88)90008-3
更新日期:1988-09-20 00:00:00
abstract::Telomeres are dynamic nucleoprotein structures that cap the ends of eukaryotic chromosomes. In humans, the long (TTAGGG)(n) double-stranded telomeric DNA repeats are bound specifically by the two related proteins TRF1 and TRF2, and are organized in nucleosomes. Whereas the role of TRF1 and TRF2 in telomeric function h...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.04.071
更新日期:2006-07-07 00:00:00
abstract::The prokaryotic transcription factors GreA and GreB are involved in the regulation of transcript elongation by RNA polymerase (RNAP). Their known activities include suppression of transcription arrest, enhancement of transcription fidelity, and facilitation of the transition from abortive initiation to productive elon...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1545
更新日期:1998-02-20 00:00:00