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1,051
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
, 2007
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Solvent mediated interactions in the structure of the nucleosome core particle at
, 2002
"... Solvent binding in the nucleosome core particle containing a 147 base pair, defined-sequence DNA is characterized from the X-ray crystal structure at 1.9 A ˚ resolution. A single-base-pair increase in DNA length over that used previously results in substantially improved clarity of the electron dens ..."
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Cited by 134 (9 self)
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Solvent binding in the nucleosome core particle containing a 147 base pair, defined-sequence DNA is characterized from the X-ray crystal structure at 1.9 A ˚ resolution. A single-base-pair increase in DNA length over that used previously results in substantially improved clarity of the electron density and accuracy for the histone protein and DNA atomic coordinates. The reduced disorder has allowed for the first time extensive modeling of water molecules and ions. Over 3000 water molecules and 18 ions have been identified. Water molecules acting as hydrogen-bond bridges between protein and DNA are approximately equal in number to the direct hydrogen bonds between these components. Bridging water molecules have a dual role in promoting histone–DNA association not only by providing further stability to direct protein–DNA interactions, but also by enabling formation of many additional interactions between more distantly related elements. Water molecules residing in the minor groove play an important role in facilitating insertion of arginine side-chains. Water structure at the interface of the histones and DNA provides a means of accommodating intrinsic DNA conformational variation, thus limiting the sequence dependency of nucleosome positioning while enhancing mobility. Monovalent anions are bound near the N termini of histone a-helices that are not occluded by DNA phosphate groups. Their location in proximity to the DNA phosphodiester backbone suggests that they damp the electrostatic interaction between the histone proteins and the DNA. Divalent cations are bound at specific sites in the nucleosome core particle and contribute to histone–histone and histone–DNA interparticle interactions. These interactions may be relevant to nucleosome association in arrays.
Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation
- J. Mol. Biol
, 1999
"... Small-probe contact dot surface analysis, with all explicit hydrogen atoms added and their van der Waals contacts included, was used to choose between the two possible orientations for each of 1554 asparagine (Asn) and glutamine (Gln) side-chain amide groups in a dataset of 100 unrelated, high-quali ..."
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Cited by 117 (17 self)
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Small-probe contact dot surface analysis, with all explicit hydrogen atoms added and their van der Waals contacts included, was used to choose between the two possible orientations for each of 1554 asparagine (Asn) and glutamine (Gln) side-chain amide groups in a dataset of 100 unrelated, high-quality protein crystal structures at 0.9 to 1.7 AÊ resolution. For the movable-H groups, each connected, closed set of local H-bonds was optimized for both H-bonds and van der Waals overlaps. In addition to the Asn/Gln ``¯ips'', this process included rotation of OH, SH, NH 3, and methionine methyl H atoms, ¯ip and protonation state of histidine rings, interaction with bound ligands, and a simple model of water interactions. However, except for switching N and O identity for amide ¯ips (or N and C identity for His ¯ips), no non-H atoms were shifted. Even in these very high-quality structures, about 20 % of the Asn/Gln side-chains required a 180 ¯ip to optimize H-bonding and/or
Molecular basis of double-stranded RNA-protein interactions: structure of a dsRNA-binding domain complexed with dsRNA
- EMBO J
, 1998
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Weeds A. Cofilin changes the twist of F-actin: implications for actin filament dynamics and cellular function
- J Cell Biol
, 1997
"... Abstract. Cofilin is an actin depolymerizing protein found widely distributed in animals and plants. We have used electron cryomicroscopy and helical reconstruction to identify its binding site on actin filaments. Cofilin binds filamentous (F)-actin cooperatively by bridging two longitudinally assoc ..."
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Cited by 72 (1 self)
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Abstract. Cofilin is an actin depolymerizing protein found widely distributed in animals and plants. We have used electron cryomicroscopy and helical reconstruction to identify its binding site on actin filaments. Cofilin binds filamentous (F)-actin cooperatively by bridging two longitudinally associated actin subunits. The binding site is centered axially at subdomain 2 of the lower actin subunit and radially at the cleft between subdomains 1 and 3 of the upper actin subunit. Our work has revealed a totally unexpected (and unique) property of cofilin, namely, its ability to change filament twist. As a consequence of this change in twist, filaments decorated with cofilin have much shorter ‘actin crossovers ’ (�75 % of those normally observed in F-actin structures). Although their binding sites are distinct, cofilin and phalloidin do not bind simultaneously to F-actin. This is the first demonstration of a protein that excludes another actin-binding molecule by changing filament twist. Alteration of F-actin structure by cofilin/ADF appears to be a novel mechanism through which the actin cytoskeleton may be regulated or remodeled. Please address all correspondence to Dr. Amy McGough, Verna and
Recognition of spatial motifs in protein structures
- Journal of Molecular Biology
, 1999
"... As the structural database continues to expand, new methods are required to analyse and compare protein structures. Whereas the recog-nition, comparison, and classification of folds is now more or less a solved problem, tools for the study of constellations of small numbers of residues are few and f ..."
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Cited by 65 (1 self)
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As the structural database continues to expand, new methods are required to analyse and compare protein structures. Whereas the recog-nition, comparison, and classification of folds is now more or less a solved problem, tools for the study of constellations of small numbers of residues are few and far between. In this paper, two programs are described for the analysis of spatial motifs in protein structures. The first, SPASM, can be used to find the occurrence of a motif consisting of arbi-trary main-chain and/or side-chains in a database of protein structures. The program also has a unique capability to carry out ‘‘fuzzy pattern matching’ ’ with relaxed requirements on the types of some or all of the matching residues. The second program, RIGOR, scans a single protein structure for the occurrence of any of a set of pre-defined motifs from a database. In one application, spatial motif recognition combined with profile analysis enabled the assignment of the structural and functional class of an uncharacterised hypothetical protein in the sequence database. In another application, the occurrence of short left-handed helical segments in protein structures was investigated, and such segments were found to be fairly common. Potential applications of the techniques presented here lie in the analysis of (newly determined) structures, in comparative structural analysis, in the design and engineering of novel functional sites, and in the prediction of structure and function of unchar-acterised proteins.
Visualizing and quantifying molecular goodness-of-fit: smallprobe contact dots with explicit hydrogen atoms
- J. Mol. Biol
, 1999
"... The technique of small-probe contact dot surfaces is described as a method for calculating and displaying the detailed atomic contacts inside or between molecules. It allows one both to measure and to visualize directly the goodness-of-®t of packing interactions. It requires both highly accurate str ..."
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Cited by 59 (8 self)
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The technique of small-probe contact dot surfaces is described as a method for calculating and displaying the detailed atomic contacts inside or between molecules. It allows one both to measure and to visualize directly the goodness-of-®t of packing interactions. It requires both highly accurate structures and also the explicit inclusion of all hydrogen atoms and their van der Waals interactions. A reference dataset of 100 protein structures was chosen on the basis of resolution (1.7 AÊ or better), crystallographic R-value, non-homology, and the absence of any unusual problems. Hydrogen atoms were added in standard geometry and, where needed, with rotational optimization of OH, SH, and NH + 3 positions. Side-chain amide orientations were corrected where required by NH van der Waals clashes, as described in the accompanying paper. It was determined that, in general, methyl groups pack well in the default staggered conformation, except for the terminal methyl groups of methionine residues, which required rotational optimization. The distribution
Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein
- J. Virol. 2005
"... Dengue virus is an emerging global health threat. The major envelope glycoprotein, E, mediates viral attachment and entry by membrane fusion. Antibodies that bind but fail to neutralize noncognate serotypes enhance infection. We have determined the crystal structure of a soluble fragment of the enve ..."
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Cited by 52 (2 self)
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Dengue virus is an emerging global health threat. The major envelope glycoprotein, E, mediates viral attachment and entry by membrane fusion. Antibodies that bind but fail to neutralize noncognate serotypes enhance infection. We have determined the crystal structure of a soluble fragment of the envelope glycoprotein E from dengue virus type 3. The structure closely resembles those of E proteins from dengue type 2 and tick-borne encephalitis viruses. Serotype-specific neutralization escape mutants in dengue virus E proteins are all located on a surface of domain III, which has been implicated in receptor binding. While antibodies against epitopes in domain I are nonneutralizing in dengue virus, there are neutralizing antibodies that recognize serotype-conserved epitopes in domain II. The mechanism of neutralization for these antibodies is probably inhibition of membrane fusion. Our structure shows that neighboring glycans on the viral surface are spaced widely enough (at least 32 Å) that they can interact with multiple carbohydrate recognition domains on oligomeric lectins such as DC-SIGN, ensuring maximum affinity for these putative receptors.
The molecular basis of filamin binding to integrins and competition with talin
- Mol. Cell
, 2006
"... The ability of adhesion receptors to transmit biochemical signals and mechanical force across cell membranes depends on interactions with the actin cytoskeleton. Filamins are large, actin-crosslinking proteins that connect multiple transmembrane and signaling proteins to the cytoskeleton. Here, we d ..."
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Cited by 47 (4 self)
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The ability of adhesion receptors to transmit biochemical signals and mechanical force across cell membranes depends on interactions with the actin cytoskeleton. Filamins are large, actin-crosslinking proteins that connect multiple transmembrane and signaling proteins to the cytoskeleton. Here, we describe the highresolution structure of an interface between filamin A and an integrin adhesion receptor. When bound, the integrin b cytoplasmic tail forms an extended b strand that interacts with b strands C and D of the filamin immunoglobulin-like domain (IgFLN) 21. This interface is common to many integrins, and we suggest it is a prototype for other IgFLN domain interactions. Notably, the structurally defined filamin binding site overlaps with that of the integrin-regulator talin, and these proteins compete for binding to integrin tails, allowing integrin-filamin interactions to impact talin-dependent integrin activation. Phosphothreonine-mimicking mutations inhibit filamin, but not talin, binding, indicating that kinases may modulate this competition and provide additional means to control integrin functions.
Structures of Five Antibiotics Bound at the Peptidyl
"... ding author Introduction Antibiotics are compounds of natural or synthetic origin that selectively kill or inhibit the growth of microorganisms, and many of them are sufficiently specific to be useful for the treatment of bacterial infections. A large fraction of these compounds, including many th ..."
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Cited by 44 (4 self)
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ding author Introduction Antibiotics are compounds of natural or synthetic origin that selectively kill or inhibit the growth of microorganisms, and many of them are sufficiently specific to be useful for the treatment of bacterial infections. A large fraction of these compounds, including many that are used in the clinic, are inhibitors of bacterial protein synthesis, and almost all such antibiotics interact with the ribosome. The peptidyl transferase center is the target of many of these antibiotics, which is surprising given the high-degree of conservation in that region of the ribosome, and given the need for antibiotics to target specific organisms. Since publication of atomic resolution structures of both the large and small ribosomal subunits, 1--3 several papers have appeared describing the structures of complexes between ribosomal subunits and antibiotics. 4--8 Here, we extend this series by reporting crystal structures of the complexes that form between the large riboso
