Abstract:
:Cyclin K and the closely related cyclins T1, T2a, and T2b interact with cyclin-dependent kinase 9 (CDK9) forming multiple nuclear complexes, referred to collectively as positive transcription elongation factor b (P-TEFb). Through phosphorylation of the C-terminal domain of the RNA polymerase II largest subunit, distinct P-TEFb species regulate the transcriptional elongation of specific genes that play central roles in human physiology and disease development, including cardiac hypertrophy and human immunodeficiency virus-1 pathogenesis. We have determined the crystal structure of human cyclin K (residues 11-267) at 1.5 A resolution, which represents the first atomic structure of a P-TEFb subunit. The cyclin K fold comprises two typical cyclin boxes with two short helices preceding the N-terminal box. A prominent feature of cyclin K is an additional helix (H4a) in the first cyclin box that obstructs the binding pocket for the cell-cycle inhibitor p27(Kip1). Modeling of CDK9 bound to cyclin K provides insights into the structural determinants underlying the formation and regulation of this complex. A homology model of human cyclin T1 generated using the cyclin K structure as a template reveals that the two proteins have similar structures, as expected from their high level of sequence identity. Nevertheless, their CDK9-interacting surfaces display significant structural differences, which could potentially be exploited for the design of cyclin-targeted inhibitors of the CDK9-cyclin K and CDK9-cyclin T1 complexes.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Baek K,Brown RS,Birrane G,Ladias JAdoi
10.1016/j.jmb.2006.11.057subject
Has Abstractpub_date
2007-02-16 00:00:00pages
563-73issue
2eissn
0022-2836issn
1089-8638pii
S0022-2836(06)01597-Xjournal_volume
366pub_type
杂志文章abstract::The powerful explanatory paradigm of molecular biology requiring form to co-evolve with function has again been proven successful when, over the recent two decades, a wealth of biological functions have been uncovered for RNA. Previously considered as a mere mediator of the genetic code, RNA is now acknowledged as a k...
journal_title:Journal of molecular biology
pub_type: 杂志文章,评审
doi:10.1006/jmbi.1999.3312
更新日期:1999-12-10 00:00:00
abstract::Ribosomes are large nucleoproteins of approximately 3 X 10(6) Mr. In contrast to helical or spherical nucleoproteins (viruses) of similar size (which consist of several hundred small asymmetric units reproduced by symmetry), ribosomes are completely asymmetric; therefore, the amount of structural information (defined ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(86)90366-9
更新日期:1986-11-20 00:00:00
abstract::The effect of hairpin (cruciform) size on the regulation of gene expression was investigated by cloning a series of palindromic sequences into the non-essential J-F intercistronic region of the bacteriophage phi X174 ins6 genome. Genetic stability of the insert sequence and its effect on the growth efficiency of the p...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(86)90510-3
更新日期:1986-05-20 00:00:00
abstract::A 3D reconstruction at 25 A resolution of native hemoglobin of the polychaete worm Arenicola marina was carried out from frozen-hydrated specimens examined in the electron microscope. The reconstruction volume of this large extracellular multimeric respiratory pigment appears as a hexagonal bilayer structure with ecli...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.4344
更新日期:2001-01-26 00:00:00
abstract::The three-dimensional structure of [Cd7]-metallothionein-2 from rat liver was determined in aqueous solution, using nuclear magnetic resonance spectrometry and distance geometry calculations. The experimental data provided proton-proton distance constraints from measurements of nuclear Overhauser effects, constraints ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(88)90106-4
更新日期:1988-09-05 00:00:00
abstract::Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyveri, we show that duri...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.05.029
更新日期:2008-07-18 00:00:00
abstract::The impenetrability of the blood-brain barrier (BBB) to most conventional drugs impedes the treatment of central nervous system (CNS) disorders. Interventions for diseases like brain cancer, neurodegeneration, or age-associated inflammatory processes require varied approaches to CNS drug delivery. Cystine-dense peptid...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2020.04.002
更新日期:2020-06-26 00:00:00
abstract::The folding pathways of four mutants in which bulky hydrophobic residues in the B helix of apomyoglobin (ApoMb) are replaced by alanine (I28A, L29A, I30A, and L32A) have been analyzed using equilibrium and kinetic methods employing NMR, CD, fluorescence and mass spectrometry. Hydrogen exchange pulse-labeling followed ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2003.09.042
更新日期:2003-11-21 00:00:00
abstract::Increasing evidence indicates that transcriptionally silent chromatin structure is dynamic and may change its conformation in response to external or internal stimuli. We show that growth temperature affects all three forms of transcriptional silencing in Saccharomyces cerevisiae. In general, increasing the temperatur...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.10.002
更新日期:2004-12-03 00:00:00
abstract::Translocation of the majority of mitochondrial proteins from the cytosol into mitochondria requires the cooperation of TOM and TIM23 complexes in the outer and inner mitochondrial membranes. The molecular mechanisms underlying this cooperation remain largely unknown. Here, we present biochemical and genetic evidence t...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2014.07.015
更新日期:2015-03-13 00:00:00
abstract::Residues specifying aminoacylation by yeast tyrosyl-tRNA synthetase (TyrRS) of the tRNA-like structure present at the 3'-end of brome mosaic virus (BMV) RNA were determined by the in vitro approach using phage T7 transcripts. They correspond to nucleotides equivalent to base-pair C1-G72 and discriminator base A73 in t...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2001.4654
更新日期:2001-06-01 00:00:00
abstract::The average structural and dynamic properties of tetragonal hen egg-white lysozyme have been compared, in structures refined at 1.9 A resolution, using data collected at 100 K and 298 K. The molecule expands by 1.8% over this temperature range with the expansion occurring primarily in its small sub-atomic-sized spaces...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(05)80034-8
更新日期:1994-01-07 00:00:00
abstract::Membrane-bound proteases are involved in various regulatory functions. Our previous study indicated that the N-terminal region of an open reading frame, PH1510 (residues 16-236, designated as 1510-N) from the hyperthermophilic archaeon Pyrococcus horikoshii, is a serine protease with a catalytic Ser-Lys dyad that spec...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.02.052
更新日期:2006-05-12 00:00:00
abstract::Addition of the antimitotic drug vinblastine to solutions of purified tubulin induces the formation of helical polymers whose structure and type of aggregation is determined by the concentration of magnesium. While paracrystalline arrangements of single coils are observed at low concentrations of the ion, for concentr...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1995.0628
更新日期:1995-12-01 00:00:00
abstract::Retroviral proteases are translated as a part of Gag-related polyproteins, and are released and activated during particle release. Mason-Pfizer monkey virus (M-PMV) Gag polyproteins assemble into immature capsids within the cytoplasm of the host cells; however, their processing occurs only after transport to the plasm...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.11.005
更新日期:2007-02-02 00:00:00
abstract::14-3-3 proteins have been shown to regulate the actin cytoskeleton remodeling, cell adhesion and migration. In this study, we identified ezrin, a cross-linker between plasma membrane and actin cytoskeleton, as a novel 14-3-3ζ interacting partner. The direct interaction between 14-3-3ζ and ezrin was validated in the ce...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2014.06.021
更新日期:2014-09-09 00:00:00
abstract::The exon junction complex (EJC) is a macromolecular complex deposited at splice junctions on mRNAs as a consequence of splicing. At the core of the EJC are four proteins: eIF4AIII, a member of the DExH/D-box family of NTP-dependent RNA binding proteins, Y14, Magoh, and MLN51. These proteins form a stable heterotetrame...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.05.049
更新日期:2006-07-21 00:00:00
abstract::Protein denatured states are the origin of both healthy and toxic conformational species. Denatured states of ultrafast folding proteins are of interest in mechanistic studies because they are energetically close to the kinetic bottleneck of folding. However, their transient nature makes them elusive to experiment. He...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2015.08.007
更新日期:2015-09-25 00:00:00
abstract::We have studied in reconstitution experiments the conditions under which peptides derived from histones H1 and H5 are bound in chromatin and to what extent they are involved in the organization of chromatin fibers. The fragments of rat liver histone H1 (rH1) and chicken erythrocytes H1 (cH1) and H5 (cH5) used were the...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(83)80102-8
更新日期:1983-07-05 00:00:00
abstract::Human islet amyloid polypeptide (hIAPP), which is considered the primary culprit for beta-cell loss in type 2 diabetes mellitus patients, is synthesized in beta-cells of the pancreas from its precursor pro-islet amyloid polypeptide (proIAPP), which may be important in early intracellular amyloid formation as well. We ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.04.077
更新日期:2009-06-26 00:00:00
abstract::The decrease in conformational stability, delta(delta G), has been measured for 72 aliphatic side-chain mutants from four proteins in which a larger side-chain is replaced by a smaller side-chain so that steric effects are minimal. When these delta(delta G) values are corrected to the same accessibility, namely 100% b...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)90121-y
更新日期:1992-07-05 00:00:00
abstract::Ras GTPase mediates several cellular signal transduction pathways and is found mutated in a large number of cancers. It is active in the GTP-bound state, where it interacts with effector proteins, and at rest in the GDP-bound state. The catalytic domain is tethered to the membrane, with which it interacts in a nucleot...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2013.10.036
更新日期:2014-02-06 00:00:00
abstract::Phosphorylation of short linear peptide motifs is a widespread process for the dynamic regulation of protein-protein interactions. However, the global impact of phosphorylation events on the protein-protein interactome is rarely addressed. The disordered C-terminal tail of ribosomal S6 kinase 1 (RSK1) binds to PDZ dom...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2019.01.038
更新日期:2019-03-15 00:00:00
abstract::Molten globules are partially structured protein folding intermediates that adopt a native-like overall backbone topology in the absence of extensive detectable tertiary interactions. It is important to determine the extent of specific tertiary structure present in molten globules and to understand the role of specifi...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.1825
更新日期:1998-07-03 00:00:00
abstract::Erythropoietin (Epo) is the humoral regulator of red blood-cell production. Low oxygen tension increases the Epo levels by enhancing transcription, through the hypoxia-inducible factor (HIF)-1, a transcriptional modulator in oxygen-regulated gene expression. In the present work, a cooperative interaction between hypox...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2003.12.023
更新日期:2004-02-06 00:00:00
abstract::beta-1,4-Galactosyltransferase-I (beta4Gal-T1) transfers galactose from UDP-galactose to N-acetylglucosamine (GlcNAc) residues of the branched N-linked oligosaccharide chains of glycoproteins. In an N-linked biantennary oligosaccharide chain, one antenna is attached to the 3-hydroxyl-(1,3-arm), and the other to the 6-...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.07.050
更新日期:2005-10-14 00:00:00
abstract::In vivo, proteins occur in widely different physio-chemical environments, and, from in vitro studies, we know that protein structure can be very sensitive to environment. However, theoretical studies of protein structure have tended to ignore this complexity. In this paper, we have approached this problem by grouping ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1498
更新日期:1998-02-20 00:00:00
abstract::Set8 is the only mammalian monomethyltransferase responsible for H4K20me1, a methyl mark critical for genomic integrity of eukaryotic cells. We present here a structural model for how Set8 uses multivalent interactions to bind and methylate the nucleosome based on crystallographic and solution studies of the Set8/nucl...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2016.02.025
更新日期:2016-04-24 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::Three ribosomal RNA mutations conferring resistance to the antibiotic kasugamycin were isolated using a strain of Escherichia coli in which all of the rRNA is transcribed from a plasmid-encoded rrn operon. The mutations, A794G, G926A, and A1519C, mapped to universally conserved sites in the 16 S RNA gene. Site-directe...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.3160
更新日期:1999-10-15 00:00:00