QM/MM study of energy storage and molecular rearrangements due to the primary event in vision

The energy storage and the molecular rearrangements due to the primary photochemical event in rhodopsin are investigated by using quantum mechanics/molecular mechanics hybrid methods in conjunction with high-resolution structural data of bovine visual rhodopsin. The analysis of the reactant and product molecular structures reveals the energy storage mechanism as determined by the detailed molecular rearrangements of the retinyl chromophore, including rotation of the (C11-C12) dihedral angle from -11 degrees in the 11-cis isomer to -161 degrees in the all-trans product, where the preferential sense of rotation is determined by the steric interactions between Ala-117 and the polyene chain at the C13 position, torsion of the polyene chain due to steric constraints in the binding pocket, and stretching of the salt bridge between the protonated Schiff base and the Glu-113 counterion by reorientation of the polarized bonds that localize the net positive charge at the Schiff-base linkage. The energy storage, computed at the ONIOM electronic-embedding approach (B3LYP/6-31G*:AMBER) level of theory and the S0-->S1 electronic-excitation energies for the dark and product states, obtained at the ONIOM electronic-embedding approach (TD-B3LYP/6-31G*//B3LYP/6-31G*:AMBER) level of theory, are in very good agreement with experimental data. These results are particularly relevant to the development of a first-principles understanding of the structure-function relations in prototypical G-protein-coupled receptors.     

Structural enzymology of cholesterol biosynthesis and storage

Cholesterol biosynthesis occurs in the endoplasmic reticulum (ER). Its lego-like construction from water-soluble small metabolites via intermediates of increasing complexity to water-insoluble cholesterol requires numerous distinct enzymes. Dysfunction of the involved enzymes can cause several human inborn defects and diseases. Here, we review recent structures of three key cholesterol biosynthetic enzymes: Squalene epoxidase (SQLE), NAD(P)-dependent steroid dehydrogenase-like (NSDHL), and 3β-hydroxysteroid Δ⁸-Δ⁷ isomerase termed EBP. Moreover, we discuss structures of acyl-CoA:cholesterol acyltransferase (ACAT) enzymes, which are responsible for forming cholesteryl esters from cholesterol to maintain cholesterol homeostasis in the ER. The structures of these enzymes reveal their catalytic mechanism and provide a molecular basis to develop drugs for treating diseases linked to their dysregulation.     

Iron chaperones for mitochondrial Fe-S cluster biosynthesis and ferritin iron storage

Protein controlled iron homeostasis is essential for maintaining appropriate levels and availability of metal within cells. Recently, two iron chaperones have been discovered that direct metal within two unique pathways: (1) mitochondrial iron-sulfur (Fe-S) cluster assembly and (2) within the ferritin iron storage system. Although structural and functional details describing how these iron chaperones operate are emerging, both share similar iron binding affinities and metal-ligand site structures that enable them to bind and release Fe2+ to specific protein partners. Molecular details related to iron binding and delivery by these chaperones will be explored within this review.     

Control of cholesterol biosynthesis,uptake and storage in hepatocytes by Cideb

Cideb, a member of CIDE family proteins, has emerged as an important regulator in the development of obesity and diabetes by controlling fatty acid synthesis and VLDL secretion in hepatocytes. Here, we investigated the role of Cideb in cholesterol biosynthesis, uptake and storage in the liver by using Cideb-null mice as a model system. Cideb-null mice and wild-type mice were treated with normal diet (ND) or high cholesterol diet (HCD) for one month. The metabolic parameters of cholesterol metabolism and expression profiles of genes in cholesterol biosynthesis and storage were measured. Cideb-null mice had lower levels of plasma cholesterol and LDL when fed with both ND and HCD and increased rate of cholesterol absorption. Furthermore, the liver of Cideb-null mice has lower rates of cholesterol biosynthesis and reduced expression levels of sterol response element-binding protein (SREBP) cleavage-activation protein (SCAP), and lower levels of nuclear form of SREBP2 and its downstream target genes in cholesterol biosynthesis pathway under a normal diet treatment. On the contrary, hepatic cholesterol biosynthesis rate between wild-type and Cideb-null mice was similar after high cholesterol diet treatment. Interestingly, hepatic cholesterol storage in the liver of Cideb-null mice was significantly increased due to its increased LDL receptor (LDLR) and acyl-CoA cholesterol acyltransferase (ACAT) expression. Finally, we observed drastically reduced cholesterol levels in the heart of Cideb-null mice fed with a high cholesterol diet. Overall, our data suggest that Cideb is a novel regulator in controlling cholesterol homeostasis in the liver. Therefore, Cideb could serve as an important therapeutical target for the treatment of atherosclerosis and cardiovascular diseases.     

Photosynthetic energy storage efficiency,oxygen evolution and chloroplast movement

When there is a saturating supply of dissolved carbon available, photosynthetic energy storage efficiency (ES) varies linearly with light fluence rate (I) for both Vallisneria americana and Pisum sativum leaves. The frequently reported hyperbolic relationship between ES and I occurs only when low levels of dissolved carbon are present in the medium. The linear relationship has its origin in intracellular events and implies that two heat-producing processes limit the value of ES. The rate of one process varies as I and the other varies as I². The rates of both processes were changed after a 2 hour exposure to 400 μmol photons m⁻² s⁻¹ of red light, speeding up the process that depends linearly on I and slowing the other. Illumination for 1 hour with 100 μmol photons m⁻² s⁻¹ of blue (but not red) light moves many chloroplasts from the periclinal to the anticlinal cell walls [Inoue and Shibata (1973) Planta 114: 341–358]. Blue light exposure of V. americana leaf sections (a) reduced the rate of oxygen evolution under light-limiting conditions by about 22%; (b) increased the value of ES by an amount dependent on the light fluence rate; and (c) decreased the slope of (ES v I). The slope change indicated that light absorption had fallen by 26% after blue light exposure. The rate of oxygen evolution (V) was measured under light-limiting conditions with leaf sections in which the chloroplasts had been immobilised after blue or red light exposure. With both red and blue-exposed leaf sections, V fell by about 50% after exposure to 1 hour of 1250 μmol photons m⁻² s⁻¹ of white light. Thus accumulation of chloroplasts on anticlinal walls did not protect the leaf from photoinactivation by a high light fluence rate. This revised version was published online in August 2006 with corrections to the Cover Date.     

光受体及光信号转导

植物在进化过程中形成了对环境信号反应的能力,光是植物生长发育中的一个重要的环境信号.植物为了更好地生长和发育形成了精密的光信号接收和转导系统.本文介绍近年来光信号接收即光受体和光信号的转导研究进展.     

光受体及光信号转导

植物在进化过程中形成了对环境信号反应的能力,光是植物生长发育中的一个重要的环境信号。植物为了更好地生长和发育形成了精密的光信号接收和转导系统。本文介绍近年来光信号接收即光受体和光信号的转导研究进展。     

Histamine: A Neurotransmitter Candidate for Drosophila Photoreceptors

Recent experimental evidence suggests that histamine might be the synaptic transmitter used by invertebrate photoreceptors. In the present study, we have examined whether histamine is a transmitter candidate for Drosophila photoreceptors. Our findings are as follows: (a) Large amounts of histamine are synthesized by wild-type heads, whereas heads from the eye-deficient mutants, eyes absent and sine oculis, show reduced histamine synthesis. (b) Histidine decarboxylase activity is approximately 10-fold higher in extracts of normal heads compared with that in the mutants. (c) Histamine taken up by fly heads is metabolized into N-acetylhistamine and imidazole-4-acetic acid. (d) Immunostaining of normal and sevenless heads with histamine-specific antisera demonstrates that histamine is present in photoreceptors R1-6 and R8. (e) Histamine synthesized from exogenously supplied [3H]histidine can be released by depolarization with 50 mM K+, and the release is Ca2+ dependent. These observations strongly suggest that histamine is a major neurotransmitter used by Drosophila photoreceptors.     

Free energy and time economy for the mutual selection of monomers in biosynthesis, primarily protein synthesis

The starting point of this work is the fact that the correction of errors in biosynthesis must be paid for by an increased dissipation (free energy loss) or a time delay. Further, a low accuracy is wasteful in this respect as the cell then produces a number of non-functioning products with a significant "production cost". One can then look for the situations of best "economy" for the selection processes. This is particularly obvious in reciprocal selections, where in some cases a substrate A shall be selected but discriminated against a competitor B, and in other cases, the opposite is true, B shall be selected with A as a competitor. It can be expected only in certain symmetric situations that these reciprocal selections are made in an equal way. Because one substrate shall be selected more often or it may be more relevant for the product, it may occur in higher concentrations and/or be selected more accurately (at a higher cost). The opposite selection may then be less accurate. The work studies various aspects of this.     

Photoreceptors of Bryozoan Larvae (Cheilostomata, Cellularioidea)

The ultrastructure of potential photoreceptors in larvae of Tricellaria occidentalis and four species of Bugula is described and compared with previously reported photoreceptors in larvae of Bugula neritina and Scrupocellaria bertholetti. A single sensory cell forms the functional unit of each photoreceptor. This cell is distinguished by a concentration of pigment vesicles in its apical part, a direct connection with the nervous system, and a large number of cilia that form the photoreceptoral organelle. These cilia have axonemes morphologically identical to those of motile cilia. The membranes of sensory cilia are unbeaded and qualitatively less osmophilic than those of the motile cilia of adjacent accessory and coronal cells. Three photoreceptor types are designated based on topological complexity: Type I, in which the sensory cell is flush with adjacent coronal cells and the photoreceptoral organelle is unprotected; Type II, in which the apical surface of the sensory cell is invaginated, forming a lumen containing the photoreceptoral organelle; and Type III, in which the sensory cell is at the base of an epidermal invagination and the photoreceptoral organelle is protected in a lumen formed by the sensory cell and accessory cells. There is a greater range of morphological variation among photoreceptors in larvae of Bugula spp. than between those of two species of the related genera Scrupocellaria and Tricellaria.     

Complete assignment of the hydrogen out-of-plane wagging vibrations of bathorhodopsin: chromophore structure and energy storage in the primary photoproduct of vision

Resonance Raman vibrational spectra of the retinal chromophore in bathorhodopsin have been obtained after regenerating bovine visual pigments with an extensive series of 13C- and deuterium-labeled retinals. A low-temperature spinning cell technique was used to produce high-quality bathorhodopsin spectra exhibiting resolved hydrogen out-of-plane wagging vibrations at 838, 850, 858, 875, and 921 cm-1. The isotopic shifts and a normal coordinate analysis permit the assignment of these lines to the HC7 = C8H Bg, C14H, C12H, C10H, and C11H hydrogen out-of-plane wagging modes, respectively. The coupling constant between the C11H and C12H wags as well as the C12H wag force constant are unusually low compared to those of retinal model compounds. This quantitatively confirms the lack of coupling between the C11H and C12H wags and the low C12H wag vibrational frequency noted earlier by Eyring et al. [(1982) Biochemistry 21, 384]. The force constants for the C10H and C14H wags are also significantly below the values observed in model compounds. We suggest that the perturbed hydrogen out-of-plane wagging and C-C stretching force constants for the C10-C11 = C12-C13 region of the chromophore in bathorhodopsin result from electrostatic interactions with a charged protein residue. This interaction may also contribute to the 33 kcal/mol energy storage in bathorhodopsin.