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Neuroglobin, mainly expressed in vertebrate brain and retina, is a recently identified member of the globin superfamily. Augmenting O 2 supply, neuroglobin promotes survival of neurons upon hypoxic injury, potentially limiting brain damage. In the absence of exogenous ligands, neuroglobin displays a hexacoordinated heme. O 2 and CO bind to the heme iron, displacing the endogenous HisE7...
Signaling in apoptosis and inflammation is often mediated by proteins of the death domain superfamily in the Fas/FADD/Caspase-8 or the Apaf-1/Caspase-9 pathways. This superfamily currently comprises the death domain (DD), death effector domain (DED), caspase recruitment domain (CARD), and pyrin domain (PYD) subfamilies. The PYD subfamily is most abundant, but three-dimensional structures are only...
The structures of double-stranded RNA viruses infecting mammals and insects have been previously determined. Now the structure of the plant rice dwarf virus reveals common themes and novel features among the reoviruses.
Rice dwarf virus (RDV), the causal agent of rice dwarf disease, is a member of the genus Phytoreovirus in the family Reoviridae. RDV is a double-shelled virus with a molecular mass of approximately 70 million Dalton. This virus is widely prevalent and is one of the viruses that cause the most economic damage in many Asian countries. The atomic structure of RDV was determined at 3.5 A resolution by...
The neural cell adhesion molecule, NCAM, mediates Ca 2+ -independent cell-cell and cell-substratum adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM molecules) binding. NCAM plays a key role in neural development, regeneration, and synaptic plasticity, including learning and memory consolidation. The crystal structure of a fragment comprising the three N-terminal Ig...
The crystal structure of sulfite oxidase from Arabidopsis thaliana provides a physical picture of a new molybdenum enzyme, the first such from plants and the simplest one yet identified from a eukaryotic source.
Actin is one of the most conserved and versatile proteins capable of forming homopolymers and interacting with numerous other proteins in the cell. We performed an alanine mutagenesis scan covering the entire β-actin molecule. Somewhat surprisingly, the majority of the mutants were capable of reaching a stable conformation. We tested the ability of these mutants to bind to various actin binding proteins,...
Borna disease virus (BDV) causes an infection of the central nervous system in a wide range of vertebrates, which can fatally progress to an immune-mediated disease, called Borna disease. BDV is a member of the Mononegavirales, which also includes the highly infectious measles and Ebola viruses. The viral nucleoproteins are central to transcription, replication, and packaging of the RNA genome. We...
Pneumococcal bacteriophage-encoded lysins are modular choline binding proteins that have been shown to act as enzymatic antimicrobial agents (enzybiotics) against streptococcal infections. Here we present the crystal structures of the free and choline bound states of the Cpl-1 lysin, encoded by the pneumococcal phage Cp-1. While the catalytic module displays an irregular (β/α) 5 β 3 ...
The atomic structure of the Borna-disease virus nucleocapsid protein represents the first detailed structural information for such essential element in the negative-stranded RNA virus replication machine.
New structures of LD motifs bound to the focal adhesion targeting domain show that the motifs are recognized as amphipathic α helices. The structures highlight the structural and functional diversity of leucine and aspartic acid-based targeting motifs.
Crystal structures of equine herpesvirus type-4 thymidine kinase (EHV4-TK) in complex with (i) thymidine and ADP, (ii) thymidine and SO 4 and the bisubstrate analogs, (iii) TP 4 A, and (iv) TP 5 A have been solved. Additionally, the structure of herpes simplex virus type-1 thymidine kinase (HSV1-TK) in complex with TP 5 A has been determined. These are the first structures...
The first structure of a pyrin domain confirms its membership in the death domain superfamily, reveals a local unfolding of the third of six helices, and suggests that the folding/unfolding transition of this helix may be an important determinant of the function and disease related dysfunction of this domain.
A global mutagenesis survey of actin structure and function shows that many mutants retain the ability to polymerize despite its very high sequence conservation.
Calmodulin has been a subject of intense scrutiny since its discovery because of its unusual properties in regulating the functions of about 100 diverse target enzymes and structural proteins. The original and to date only crystal conformation of native eukaryotic Ca 2+ -calmodulin (Ca 2+ -CaM) is a very extended molecule with two widely separated globular domains linked...
The molybdenum cofactor (Moco) containing sulfite oxidase (SO) from Arabidopsis thaliana has recently been identified and biochemically characterized. The enzyme is found in peroxisomes and believed to detoxify excess sulfite that is produced during sulfur assimilation, or due to air pollution. Plant SO (PSO) is homodimeric and homologous to animal SO, but contains only a single Moco domain without...
Focal adhesions (FAs) are large submembrane signaling complexes formed at sites of cellular attachment to the extracellular matrix. The interaction of LD motifs with their targets plays an important role in the assembly of FAs. We have determined the molecular basis for the recognition of two paxillin LD motifs by the FA targeting (FAT) domain of FA kinase using a combination of X-ray crystallography,...
Crystal structures of the eukaryotic pore-forming toxin sticholysin II, its complex with phosphocholine, and electron microscopy of 2D crystals on lipid monolayer give insights into the sequential steps of the actinoporin membrane penetration.
Sco1, a protein required for the proper assembly of cytochrome c oxidase, has a soluble domain anchored to the cytoplasmic membrane through a single transmembrane segment. The solution structure of the soluble part of apoSco1 from Bacillus subtilis has been solved by NMR and the internal mobility characterized. Its fold places Sco1 in a distinct subgroup of the functionally unrelated thioredoxin proteins...
Sir2 proteins are NAD + -dependant protein deactylases that have been implicated in playing roles in gene silencing, DNA repair, genome stability, longevity, metabolism, and cell physiology. To define the mechanism of Sir2 activity, we report the 1.5 A crystal structure of the yeast Hst2 (yHst2) Sir2 protein in ternary complex with 2'-O-acetyl ADP ribose and an acetylated histone H4 peptide...
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