Abstract:
:Eukaryotes have several highly conserved actin-binding proteins that crosslink filamentous actin into compact ordered bundles present in distinct cytoskeletal processes, including microvilli, stereocilia and filopodia. Fascin is an actin-binding protein that is present predominantly in filopodia, which are believed to play a central role in normal and aberrant cell migration. An important outstanding question regards the molecular basis for the unique localization and functional properties of fascin compared with other actin crosslinking proteins. Here, we present the crystal structure of full-length Homo sapiens fascin-1, and examine its packing, conformational flexibility, and evolutionary sequence conservation. The structure reveals a novel arrangement of four tandem beta-trefoil domains that form a bi-lobed structure with approximate pseudo 2-fold symmetry. Each lobe has internal approximate pseudo 2-fold and pseudo 3-fold symmetry axes that are approximately perpendicular, with beta-hairpin triplets located symmetrically on opposite sides of each lobe that mutational data suggest are actin-binding domains. Sequence conservation analysis confirms the importance of hydrophobic core residues that stabilize the beta-trefoil fold, as well as interfacial residues that are likely to stabilize the overall fascin molecule. Sequence conservation also indicates highly conserved surface patches near the putative actin-binding domains of fascin, which conformational dynamics analysis suggests to be coupled via an allosteric mechanism that might have important functional implications for F-actin crosslinking by fascin.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Sedeh RS,Fedorov AA,Fedorov EV,Ono S,Matsumura F,Almo SC,Bathe Mdoi
10.1016/j.jmb.2010.04.043subject
Has Abstractpub_date
2010-07-16 00:00:00pages
589-604issue
3eissn
0022-2836issn
1089-8638pii
S0022-2836(10)00431-6journal_volume
400pub_type
杂志文章abstract::The cap-binding protein eIF4E is the first in a chain of translation initiation factors that recruit 40S ribosomal subunits to the 5' end of eukaryotic mRNA. During cap-dependent translation, this protein binds to the 5'-terminal m(7)Gppp cap of the mRNA, as well as to the adaptor protein eIF4G. The latter then intera...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.12.034
更新日期:2006-03-03 00:00:00
abstract::HtrA (high-temperature requirement A) family proteins play important roles in protein-quality control processes in the bacterial periplasm. A common feature of all members of this family is their modular organization comprising a chymotrypsin-like protease domain and at least one PDZ (postsynaptic density of 95 kDa, d...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2015.06.023
更新日期:2015-08-28 00:00:00
abstract::We have derived a secondary structure model for the c-myc internal ribosome entry segment (IRES) by using information from chemical probing of the c-myc IRES RNA to constrain structure prediction programs. Our data suggest that the IRES is modular in nature, and can be divided into two structural domains linked by a l...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2001.4745
更新日期:2001-06-29 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::We have previously reported the structures of the native holo and substrate-bound forms of LL-diaminopimelate aminotransferase from Arabidopsis thaliana (AtDAP-AT). Here, we report the crystal and molecular structures of the LL-diaminopimelate aminotransferase from Chlamydia trachomatis (CtDAP-AT) in the apo-form and ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2011.06.023
更新日期:2011-08-19 00:00:00
abstract::By combining anisotropy of small-angle neutron scattering (SANS) and optical anisotropy (linear dichroism, l.d.) on flow-oriented RecA-DNA complexes, the average DNA-base orientation has been determined in RecA complexes with double-stranded (ds) as well as single-stranded (ss) DNA. From the anisotropy of the two-dime...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)91060-3
更新日期:1992-08-20 00:00:00
abstract::The RuvAB and RecG proteins of Escherichia coli promote branch migration of Holliday junction intermediates in genetic recombination. Both are structure-specific helicases that unwind and rewind DNA at the junction point. The helicase activities of these proteins were investigated using RNA:DNA hybrid molecules. RuvAB...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0671
更新日期:1996-12-13 00:00:00
abstract::L-threonine dehydrogenase (TDH) is an enzyme that catalyzes the oxidation of L-threonine to 2-amino-3-ketobutyrate. We solved the first crystal structure of a medium chain L-threonine dehydrogenase from a hyperthermophilic archaeon, Pyrococcus horikoshii (PhTDH), by the single wavelength anomalous diffraction method u...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.11.060
更新日期:2007-02-23 00:00:00
abstract::Four previously isolated mutations in Salmonella phage P22 tailspike protein were used to study the relationship between protein stability, folding, and function. Tailspike protein binds and hydrolyzes the repetitive O-antigen structure in Salmonella lipopolysaccharide. Four mutations (V331G, V331A, A334V, A334I) are ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.3165
更新日期:1999-10-29 00:00:00
abstract::We have measured the solubility, and the rates of homogeneous and heterogeneous nucleation on sickle hemoglobin (HbS beta 6 Glu-->Val) additionally modified by site-directed mutagenesis to possess Ala rather than Leu at beta 88, which forms part of the receptor site for beta 6 Val in the sickle polymer. The solubility...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0749
更新日期:1997-02-07 00:00:00
abstract::The solution structure of r-elafin, a specific elastase inhibitor, has been determined using NMR spectroscopy. Characterized by a flat core and a flexible N-terminal extremity, the three-dimensional structure is formed by a central twisted beta-hairpin accompanied by two external segments linked by the proteinase bind...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.0983
更新日期:1997-05-09 00:00:00
abstract::The serine protease inhibitor (serpin) superfamily is involved in a wide range of cellular processes including fibrinolysis, angiogenesis, apoptosis, inflammation, metastasis and viral pathogenesis. Here, we investigate the unique mousetrap inhibition mechanism of serpins through saturation mutagenesis of the P8 resid...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.09.008
更新日期:2005-11-11 00:00:00
abstract::The protein composition of the various muscle types in Drosophila melanogaster has been studied quite thoroughly and the analysis has revealed many differences involving the usage of muscle specific isoforms of a given protein, as well as the presence of proteins restricted to one muscle type. Drosophila projectin, th...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.1756
更新日期:1998-05-29 00:00:00
abstract::We show here that the specific use of fast or slowly translated codons in the early coding region of a gene may influence both the mRNA stability and premature transcription termination. We first inserted a pair of nearly identical 42-base-pair (bp)-long sequences into codon 3 of the Escherichia coli lacZ gene. The on...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2019.01.026
更新日期:2019-03-15 00:00:00
abstract::Crystal structures of an Fab (NC6.8) from a murine IgG2b(kappa) antibody and its complex with a sweet-tasting, N-,N'-,N"-trisubstituted guanidine compound (NC174) have been determined by X-ray analysis. Both crystal forms are produced by a microseeding technique in polyethylene glycol (PEG) 8000 but the habits and spa...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.1133
更新日期:1994-02-11 00:00:00
abstract::The regulation of vertebrate striated muscle contraction involves a number of different molecules, including the thin-filament accessory proteins tropomyosin and troponin that provide Ca(2+)-dependent regulation by controlling access to myosin binding sites on actin. Cardiac myosin binding protein C (cMyBP-C) appears ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2011.07.056
更新日期:2011-09-23 00:00:00
abstract::Automated protein redesign, as implemented in the program ORBIT, was used to redesign the core of phage T4 lysozyme. A total of 26 buried or partially buried sites in the C-terminal domain were allowed to vary both their sequence and side-chain conformation while the backbone and non-selected side-chains remained fixe...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00856-8
更新日期:2003-09-19 00:00:00
abstract::We use a coarse-grained protein model to characterize the critical nucleus, structural stability, and fibril elongation propensity of Abeta(1-40) oligomers for the C(2x) and C(2z) quaternary forms proposed by solid-state NMR. By estimating equilibrium populations of structurally stable and unstable protofibrils, we de...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.10.011
更新日期:2007-01-12 00:00:00
abstract::The bacterial immunity proteins Im7 and Im9 fold with mechanisms of different kinetic complexity. Whilst Im9 folds in a two-state transition at pH 7.0 and 10 degrees C, Im7 populates an on-pathway intermediate under these conditions. In order to assess the role of sequence versus topology in the folding of these prote...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(02)01249-4
更新日期:2003-02-07 00:00:00
abstract::The yeast a1 and alpha 2 proteins are examples of homeodomain proteins that display cell-type-specific expression. They are co-expressed in only one type of cell, the a/alpha cell, where they repress the expression of a group of target genes. Using purified proteins, we demonstrate that a1 and alpha 2 form a highly sp...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1993.1517
更新日期:1993-10-05 00:00:00
abstract::In order to colonize a niche and compete for scarce resources, microorganisms have evolved means to adjust the expression levels of their biosynthetic enzymes in response to the changing levels of metabolites available to them. To do so, they often rely on transcription factors or structured RNAs that directly sense t...
journal_title:Journal of molecular biology
pub_type: 杂志文章,评审
doi:10.1016/j.jmb.2016.04.019
更新日期:2016-05-22 00:00:00
abstract::A database of X-ray crystal structures of double helical DNA oligomers has been used to analyse the role of the sugar-phosphate backbone in coupling the conformational properties of neighbouring dinucleotide steps. The base step parameters which are most strongly coupled to the backbone degrees of freedom are slide an...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.3237
更新日期:2000-01-07 00:00:00
abstract::Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a glycolytic enzyme that displays several non-glycolytic activities, including the maintenance and/or protection of telomeres. In this study, we determined the molecular mechanism and biological role of the interaction between GAPDH and human telomeric DNA. Using gel...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.09.062
更新日期:2009-12-11 00:00:00
abstract::The MotA protein of Escherichia coli is a component of the flagella that functions together with the MotB protein in transmembrane proton conduction. It is an integral membrane protein, with four hydrophobic segments that might traverse the membrane and two short segments that are predicted to be in the periplasm. In ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1995.0431
更新日期:1995-08-11 00:00:00
abstract::Drosophila development is regulated by two hormones, 20-hydroxyecdysone (ecdysone) and juvenile hormone. We previously found that expression of the E75 gene is induced by both hormones in cultured S2 cells. E75 occupies over 100 kb of genomic DNA; it has four alternative promoters producing isoforms E75A, E75B, E75C, ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.02.013
更新日期:2009-04-10 00:00:00
abstract::Two-dimensional (15)N-heteronuclear single-quantum coherence (HSQC) NMR studies with a di-domain (lipoyl domain+ linker+ peripheral subunit-binding domain) of the dihydrolipoyl acetyltransferase (E2) component of the pyruvate dehydrogenase complex of Bacillus stearothermophilus allowed a molecular comparison of the ne...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.11.018
更新日期:2007-02-09 00:00:00
abstract::The ion-channel-forming C-terminal fragment of colicin A binds to negatively charged lipid vesicles and provides an example of insertion of a soluble protein into a lipid bilayer. The soluble structure is known from X-ray crystallography and consists of a ten-helix bundle containing a hydrophobic helical hairpin. In t...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(91)90707-d
更新日期:1991-04-05 00:00:00
abstract::The crystal structure of muconate lactonizing enzyme has been solved at 3 A resolution, and an unambiguous alpha-carbon backbone chain trace made. The enzyme contains three domains; the central domain is a parallel-stranded alpha-beta barrel, which has previously been reported in six other enzymes, including triose ph...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(87)90723-6
更新日期:1987-03-05 00:00:00
abstract::Alpha-tocopherol transfer protein (alpha-TTP) is a liver protein responsible for the selective retention of alpha-tocopherol from dietary vitamin E, which is a mixture of alpha, beta, gamma, and delta-tocopherols and the corresponding tocotrienols. The alpha-TTP-mediated transfer of alpha-tocopherol into nascent VLDL ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00724-1
更新日期:2003-08-15 00:00:00
abstract::The movement of the bacterial insertion sequence IS1 often generates cointegrate structures in which donor and target replicons are connected by direct repeats of IS1. The experiments reported here were designed to understand how IS1 transposition is controlled. Our physical characterization of the structures of coint...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(84)90337-1
更新日期:1984-04-05 00:00:00