Ubiquitination generally serves as a signal for targeting cytoplasmic and nuclear proteins to the proteasome for subsequent degradation. Recently, evidence has accumulated indicating that ubiquitination also plays an important role in targeting integral membrane proteins for degradation by the lytic vacuole or the lysosome. This article describes a conserved protein motif, based on a sequence of the proteasomal component Rpn10/S5a, that is known to recognize ubiquitin. The presence of this motif in Eps15, Epsin and HRS, proteins involved in ligand-activated receptor endocytosis and degradation, suggest a more general role in ubiquitin recognition.
Mitochondria exist in two interconverting forms; as small isolated particles, and as extended filaments, networks or clusters connected with intermitochondrial junctions. Extended mitochondria can represent electrically united systems, which can facilitate energy delivery from the cell periphery to the cell core and organize antioxidant defence of th e cell interior when O-2 is consumed by mitochondrial clusters near the outer cell membrane, and protonic potential is transmitted to the cell core mitochondria to form ATP As to small mitochondria, they might represent a transportable form of these organelles.
mRNA profiling enables the expression levels of thousands of transcripts in a cell to be monitored simultaneously. Nevertheless, analyses in yeast and mammalian cells have demonstrated that mRNA levels alone are unreliable indicators of the corresponding protein abundances. This discrepancy between mRNA and protein levels argues for the relevance of additional control mechanisms besides transcription. As translational control is a major mechanism regulating gene expression, the use of translated mRNA in profil in g experiments might depict the proteome more closely than does the use of total mRNA. This would combine the technical potential of genomics with the physiological relevance of proteomics.
The death domain superfamily, composed of the death domain (DD), death effector domain (DED) and caspase recruitment domain (CARD) families of proteins, plays a pivotal role in signaling events that regulate apoptosis. This review compares and contrasts the ten superfamily members with known structures. In particular the two heterodimerization modes described to date, the CARD-CARD interaction between human Apaf-1 and procaspase 9, and the DD-DD interaction between Drosophila Pelle and Tube, are examined. The dimerization modes are strikingly different and, importantly, are not mutually exclusive. In fact, a trimer can be formed using both interactions.
Some herbicides act by binding to the exchangeable quinone site in the photosystem II (PSII) reaction centre, thus blocking electron transfer. In this article, it is hypothesized that the plant is killed by light-induced oxidative stress initiated by damage caused by formation of singlet oxygen in the reaction centre itself. This occurs when light-induced charge pairs in herbicide-inhibited PSII decay by a charge recombination route involving the formation of a chlorophyll triplet state that is able to activate oxygen. The binding of phenolic herbicides favours this pathway, thus increasing the efficiency of photodamage in this class of herbicides.
Why does a given protein structure form and why is this structure stable? These fundamental biochemical questions remain fascinating and challenging problems because the physical bases of the forces that govern protein structure, stability and folding are still not well understood. Now, a general concept of hydrogen bonding in proteins is emerging. This concept involves not only N-H and O-H donor groups, but also G-H, and not only N and O as acceptor groups, but also pi -systems. We postulate that the incorporation of the entirety of these interactions leads to a more complete description of the problem, and that this could provide new perspectives and possibly new answers.
It has been proposed that myoglobin (Mb), besides being an oxygen carrier, plays the role of a nitric oxide (NO) scavenger in heart and skeletal muscle. A paper reporting data obtained using perfused hearts isolated from either wild-type or Mb-knockout mice provides the first experimental evidence for this novel function of Mb. The biochemical basis underlying the effects of NO on cardiac function is outlined in this article, beginning with the idea that this gas is an inhibitor of cytochrome-c oxidase. Some of the consequences of this new role of Mb and a molecular mechanism to account for the high reactivity of oxymyoglobin with NO are also briefly discussed.
On the basis of significant sequence similarity, we have identified JmjC domains in more than 100 eukaryotic and bacterial sequences,These include human hairless, mutated in individuals with alopecia universalis, retinoblastoma-binding protein 2 and several putative chromatin-associated proteins. JmjC domains are predicted to be metalloenzymes that adopt the cupin fold, and are candidates for enzymes that regulate chromatin remodelling.
The posttranscriptional modification of messenger RNA precursors (pre-mRNAs) by base deamination can profoundly alter the physiological function of the encoded proteins. The recent identification of tRNA-specific adenosine deaminases (ADATs) has led to the suggestion that these enzymes, as well as the cytidine and adenosine deaminases acting on pre-mRNAs (CDARs and ADARs), belong to a superfamily of RNA-dependent deaminases. This superfamily might have evolved from an ancient cytidine deaminase, This article reviews the reactions catalysed by these enzymes and discusses their evolutionary relationships.
Myoglobin,the monomeric haemoprotein expressed in red muscle, is reported in biochemistry and physiology textbooks to function as an intracellular oxygen carrier and oxygen reservoir. Here, Maurizio Brunori argues that myoglobin can also play the role of intracellular scavenger of nitric oxide, an inhibitor of mitochondrial cytochrome-e oxidase, thereby protecting respiration in the skeletal muscle and the heart.
Several human disorders are caused by or associated with the deposition of protein aggregates known as amyloid fibrils, Despite the lack of sequence homology among amyloidogenic proteins, all amyloid fibrils share a common morphology. are insoluble under physiological conditions and are resistant to proteolytic degradation. Because amyloidogenic proteins are being produced continuously, eukaryotic organisms must have developed a form of proteolytic machinery capable of controlling these aggregation-prone species before their fibrillization. This article suggests that an intracellular metalloprotease called insulin-degrading enzyme (IDE) is responsible for the elimination of proteins with amyloidogenic potential and proposes a mechanism for the selectivity of the enzyme. In this respect, IDE can also be referred to as ADE: amyloid-degrading enzyme.
The structure of a soluble homopentameric homologue of the N-terminal extracellular domain of the nicotinic acetylcholine (ACh) receptor has recently been determined at the atomic level. These data reveal the three-dimensional structure of the binding site for ACh and nicotinic ligands. The ACh-binding sites are located at subunit boundaries in an equatorial position and are framed by residues previously identified in nicotinic receptors, by photoaffinity labelling and mutagenesis experiments, as being crucial for ligand binding. On this basis, a hypothetical mechanism for the allosteric transitions of the nicotinic receptors is suggested.
Sequence profile analysis was used to detect a conserved globular domain in several proteins including deltex, Trip12 and poly-ADP-ribose polymerase homologs. It was named the WWE domain after its most conserved residues and is predicted to mediate specific protein-protein interactions in ubiquitin and ADP-ribose conjugation systems.
The Nef protein of the human immunodeficiency virus is as important for disease progression:as it is perplexing in its plethora of target molecules and functions. In this article, it is proposed that the complex biology of Nef is regulated through conformational changes of the protein that are triggered by cellular location and specific interactions as Nef traffics through the infected cell.
Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes intracellular Ca2+ stores in several cell types. Ample evidence suggests that NAADP activates intracellular Ca2+ channels distinct from those that are sensitive to inositol trisphosphate and ryanodine/cyclic ADP-ribose. Recent studies in intact cells have demonstrated functional coupling ('channel chatter') between Ca2+ release pathways mediated by NAADP inositol trisphosphate and cyclic ADP-ribose. Thus, NAADP is probably an important determinant in shaping cytosolic Ca2+ signals.
Aminoacylation of tRNAs, catalyzed by 20 aminoacyl-tRNA synthetases, is responsible for establishing the genetic code. The enzymes are divided into two classes on the basis of the architectures of their active sites. Members of the two classes also differ in that they bind opposite sides of the tRNA acceptor stem. Importantly, specific pairs of synthetases - one from each class - can be docked simultaneously onto the acceptor stem. This article relates these specific pairings to the organization of the table of codons that defines the universal genetic code.
General Protein/Mass Analysis for Windows (GPMAW) is a valuable piece of software for any molecular biologist, biochemist or mass spectrometrist wishing to analyze protein or peptide sequences. All steps from the acquisition of protein sequence from a built-in web interface, to proteolytic digests, theoretical peptide fragmentation, detailed annotation of sequences and secondary structure prediction, can be performed rapidly and intuitively without first having to spend days reading manuals.