Crystal structure of alpha 1: implications for protein design

X-ray diffraction shows the structure of a synthetic protein model, formed from noncovalent self-association of a 12-residue peptide and of sulfate ions at low pH. This peptide is a fragment of a 16-residue polypeptide that was designed to form an amphiphilic alpha helix with a ridge of Leu residues along one helical face. By interdigitation of the leucines of four such helices, the design called for self-association into a four-alpha-helical bundle. The crystal structure (2.7 angstrom resolution; R factor = 0.215) reveals a structure more complex than the design, with both a tetramer and a hexamer. The alpha-helical tetramer with leucine interior has more oblique crossing angles than most four-alpha-helical bundles; the hexamer has a globular hydrophobic core of 12 leucine residues and three associated sulfate ions. Computational analysis suggests that the hexameric association is tighter than the tetrameric one. The consistency of the structure with the design is discussed, as well as the divergence.     

The crystal structure of human Argonaute2

Argonaute proteins form the functional core of the RNA-induced silencing complexes that mediate RNA silencing in eukaryotes. The 2.3 angstrom resolution crystal structure of human Argonaute2 (Ago2) reveals a bilobed molecule with a central cleft for binding guide and target RNAs. Nucleotides 2 to 6 of a heterogeneous mixture of guide RNAs are positioned in an A-form conformation for base pairing with target messenger RNAs. Between nucleotides 6 and 7, there is a kink that may function in microRNA target recognition or release of sliced RNA products. Tandem tryptophan-binding pockets in the PIWI domain define a likely interaction surface for recruitment of glycine-tryptophan-182 (GW182) or other tryptophan-rich cofactors. These results will enable structure-based approaches for harnessing the untapped therapeutic potential of RNA silencing in humans.     

Argonaute蛋白结构及其在植物中的研究进展

在真核细胞中,许多小的非编码RNA与Argonaute蛋白结合形成RNA诱导沉默复合体,并通过识别互补的靶标RNA来调控基因表达,此过程叫RNA干扰。在植物的RNA干扰途径中,Argonaute-sRNA复合物可以通过多种不同的机制发挥作用,进而参与病原体防御、植物发育调控等关键的生物过程。综述了Argonaute蛋白的分类和结构特征、在植物体中参与RNA干扰的机制及生物学功能等研究进展。     

The three-dimensional structure of canine parvovirus and its functional implications

The three-dimensional atomic structure of a single-stranded DNA virus has been determined. Infectious virions of canine parvovirus contain 60 protein subunits that are predominantly VP-2. The central structural motif of VP-2 has the same topology (an eight-stranded antiparallel beta barrel) as has been found in many other icosahedral viruses but represents only about one-third of the capsid protein. There is a 22 angstrom (A) long protrusion on the threefold axes, a 15 A deep canyon circulating about each of the five cylindrical structures at the fivefold axes, and a 15 A deep depression at the twofold axes. By analogy with rhinoviruses, the canyon may be the site of receptor attachment. Residues related to the antigenic properties of the virus are found on the threefold protrusions. Some of the amino termini of VP-2 run to the exterior in full but not empty virions, which is consistent with the observation that some VP-2 polypeptides in full particles can be cleaved by trypsin. Eleven nucleotides are seen in each of 60 symmetry-related pockets on the interior surface of the capsid and together account for 13 percent of the genome.     

C-cadherin ectodomain structure and implications for cell adhesion mechanisms

Cadherins are transmembrane proteins that mediate adhesion between cells in the solid tissues of animals. Here we present the 3.1 angstrom resolution crystal structure of the whole, functional extracellular domain from C-cadherin, a representative "classical" cadherin. The structure suggests a molecular mechanism for adhesion between cells by classical cadherins, and it provides a new framework for understanding both cis (same cell) and trans (juxtaposed cell) cadherin interactions. The trans adhesive interface is a twofold symmetric interaction defined by a conserved tryptophan side chain at the membrane-distal end of a cadherin molecule from one cell, which inserts into a hydrophobic pocket at the membrane-distal end of a cadherin molecule from the opposing cell.     

Crystal and molecular structure of acetylselenocholine iodide

The structure of acetylselenocholine iodide has been determined by x-ray crystallographic analysis. The molecule is in the trans conformation about the C-C bond of the choline residue. This conformation appears to explain the molecule's inability to give a positive cholinergic response when added to an electroplax preparation.     

萨特的自由观及其对当代人的启示

萨特存在主义哲学以人为中心,人的自由是萨特研究的核心问题。他主张人的存在即是自由,选择体现着自由,自由选择要承担责任。在当代社会,萨特给我们很多有益的启示。     

Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation

Direct interaction between platelet receptor glycoprotein Ibalpha (GpIbalpha) and thrombin is required for platelet aggregation and activation at sites of vascular injury. Abnormal GpIbalpha-thrombin binding is associated with many pathological conditions,including occlusive arterial thrombosis and bleeding disorders. The crystal structure of the GpIbalpha-thrombin complex at 2.6 angstrom resolution reveals simultaneous interactions of GpIbalpha with exosite I of one thrombin molecule,and with exosite II of a second thrombin molecule. In the crystal lattice,the periodic arrangement of GpIbalpha-thrombin complexes mirrors a scaffold that could serve as a driving force for tight platelet adhesion. The details of these interactions reconcile GpIbalpha-thrombin binding modes that are presently controversial,highlighting two distinct interfaces that are potential targets for development of novel antithrombotic drugs.     

Crystal structure of human enterovirus 71

Enterovirus 71 is a picornavirus associated with fatal neurological illness in infants and young children. Here, we report the crystal structure of enterovirus 71 and show that, unlike in other enteroviruses, the "pocket factor," a small molecule that stabilizes the virus, is partly exposed on the floor of the "canyon." Thus, the structure of antiviral compounds may require a hydrophilic head group designed to interact with residues at the entrance of the pocket.     

Crystal and molecular structure of a thymine-thymine adduct

Thymine-thymine adduct is a product isolated from thymine irradiated with ultraviolet light in frozen aqueous solution. This compound is presumably formed through the rearrangement of an initial photoproduct. Single crystal x-ray diffraction analysis has confirmed the molecular formula of the adduct, 5-hydroxy-6-4'-(5'-methylpyrimid-2'-one)-dihydrothymine, except for the possibility of a hydrogen atom on the 3' nitrogren rather than the 1' nitrogen, and has established the stereoconfiguration of the molecule.     

Crystal and molecular structure of a pentagonal dodecahedrane

The successful synthesis of a pentagonal dodecahedrane molecule has been achieved. Obtained by a sequence of 20 stereochemically controlled steps beginning with the readily available cyclopentadienide anion, the 1,16-dimethyl derivative has D(3d) symmetry and unusual physical properties. The x-ray crystal structure shows that the alkyl groups cause only small distortions from pure dodecahedral symmetry.     

Crystal and molecular structure of a thymine phototrimer

Thymine trimer was isolated from a frozen aqueous solution of thymine which was irradiated with ultraviolet light and was presumably formed through the rearrangement of an initial oxetane photoproduct. X-ray diffraction analysis of a single crystal has confirmed the trimeric diol structure and has established the stereoconfiguration of the molecule. The possible importance of the diol structure in photobiology is pointed out.     

Crystal structure of the zeolite paulingite

Paulingite, a zeolite, has a framework structure consisting of 2016 atoms (672 silicon or aluminum and 1344 oxygen) which are in a cubic cell with an edge of length 35.093 A. The framework has several features in common with the synthetic zeolites Linde A and ZK-5; the main channels are of similar size. We have also located most of the cations and water molecules inside the frame-work.     

Crystal structure of the eukaryotic ribosome

Crystal structures of prokaryotic ribosomes have described in detail the universally conserved core of the translation mechanism. However, many facets of the translation process in eukaryotes are not shared with prokaryotes. The crystal structure of the yeast 80S ribosome determined at 4.15 angstrom resolution reveals the higher complexity of eukaryotic ribosomes, which are 40% larger than their bacterial counterparts. Our model shows how eukaryote-specific elements considerably expand the network of interactions within the ribosome and provides insights into eukaryote-specific features of protein synthesis. Our crystals capture the ribosome in the ratcheted state, which is essential for translocation of mRNA and transfer RNA (tRNA), and in which the small ribosomal subunit has rotated with respect to the large subunit. We describe the conformational changes in both ribosomal subunits that are involved in ratcheting and their implications in coordination between the two associated subunits and in mRNA and tRNA translocation.     

Crystal structure of ethylene di-11-bromoundecanoate

Ethylene di-11-bromoundecanoate, C(24)H(44)Br(2)O(4), was synthesized as a model for the hydrophobic moiety of saturated phospholipids. The crystals are monoclinic, space group P2(1)/a, with two molecules per unit cell. Unlike folded configurations proposed for phospholipids in biological membranes, the hydrocarbon chains of this diester are fully extended in the crystalline state.     

Crystal structure of Cd,Zn metallothionein

The anomalous scattering data from five Cd in the native protein were used to determine the crystal structure of cadmium, zinc (Cd,Zn) metallothionein isoform II from rat liver. The structure of a 4-Cd cluster was solved by direct methods. A 2.3 A resolution electron density map was calculated by iterative single-wavelength anomalous scattering. The structure is folded into two domains. The amino terminal domain (beta) of residues 1 to 29 enfolds a three-metal cluster of one Cd and two Zn atoms coordinated by six terminal cysteine thiolate ligands and three bridging cysteine thiolates. The carboxyl terminal domain (alpha) of residues 30 to 61 enfolds a 4-Cd cluster coordinated by six terminal and five bridging cysteine thiolates. All seven metal sites have tetrahedral coordination geometry. The domains are roughly spherical, and the diameter is 15 to 20 A; there is limited contact between domains. The folding of alpha and beta is topologically similar but with opposite chirality. Redundant, short cysteine-containing sequences have similar roles in cluster formation in both alpha and beta.     

Crystal structure of the dynein motor domain

Dyneins are microtubule-based motor proteins that power ciliary beating, transport intracellular cargos, and help to construct the mitotic spindle. Evolved from ring-shaped hexameric AAA-family adenosine triphosphatases (ATPases), dynein's large size and complexity have posed challenges for understanding its structure and mechanism. Here, we present a 6 angstrom crystal structure of a functional dimer of two ~300-kilodalton motor domains of yeast cytoplasmic dynein. The structure reveals an unusual asymmetric arrangement of ATPase domains in the ring-shaped motor domain, the manner in which the mechanical element interacts with the ATPase ring, and an unexpected interaction between two coiled coils that create a base for the microtubule binding domain. The arrangement of these elements provides clues as to how adenosine triphosphate-driven conformational changes might be transmitted across the motor domain.