肉毒神经毒素轻链的结构与功能

肉毒神经毒素(BoNT)是由肉毒梭菌产生的一类外毒素,它是目前自然界所发现的生物毒素中毒性最强的物质。近年来,BoNT制剂在临床治疗上呈现出广阔的应用前景。具有生物活性的BoNT由50kD的轻链(LC)和100kD的重链(HC)组成双链结构：LC具有锌内肽酶活性;HC为细胞结合和转位结构域。本文综述了BoNT的LC在一级结构、高级结构与功能的关系方面研究的新进展。     

东方沙蟒显微皮纹结构与功能

对隶属蟒科的东方沙蟒唇鳞的光学显微结构和扫描电镜下的超微结构的观察发现了类似小窝的结构,可能是原始的鳞片感受器官;对鳞片感受器的大小做了测量;同时观察了头部其他鳞片和身体中部背鳞和腹鳞的显微皮纹结构。所有鳞片的角皮层细胞平坦,没有大的表面特征结构,除了后缘齿状结构、微孔和窄而短的边界。考虑到穴居种类减少反光不是主要的选择因子,而主要选择是减少摩擦和清除污物,显微皮纹特征很好地符合这一假说。不同部位鳞片的差异主要表现在角皮层细胞的形状和的大小,微孔的有无,细胞后缘齿状结构的有无和大小以及细胞边界重叠的程度。首次描述了鹅卵石样多孔细胞这一微饰类型。     

Human ether-a-go-go related gene (hERG) K channels: Function and dysfunction

The human Ether-a-go-go Related Gene (hERG) potassium channel plays a central role in regulating cardiac excitability and maintenance of normal cardiac rhythm. Mutations in hERG cause a third of all cases of congenital long QT syndrome, a disorder of cardiac repolarisation characterised by prolongation of the QT interval on the surface electrocardiogram, abnormal T waves, and a risk of sudden cardiac death due to ventricular arrhythmias. Additionally, the hERG channel protein is the molecular target for almost all drugs that cause the acquired form of long QT syndrome. Advances in understanding the structural basis of hERG gating, its traffic to the cell surface, and the molecular architecture involved in drug-block of hERG, are providing the foundation for rational treatment and prevention of hERG associated long QT syndrome. This review summarises the current knowledge of hERG function and dysfunction, and the areas of ongoing research.     

Structure Driven Design of Novel Human Ether-A-Go-Go-Related-Gene Channel (hERG1) Activators

One of the main culprits in modern drug discovery is apparent cardiotoxicity of many lead-candidates via inadvertent pharmacologic blockade of K⁺, Ca²⁺ and Na⁺ currents. Many drugs inadvertently block hERG1 leading to an acquired form of the Long QT syndrome and potentially lethal polymorphic ventricular tachycardia. An emerging strategy is to rely on interventions with a drug that may proactively activate hERG1 channels reducing cardiovascular risks. Small molecules-activators have a great potential for co-therapies where the risk of hERG-related QT prolongation is significant and rehabilitation of the drug is impractical. Although a number of hERG1 activators have been identified in the last decade, their binding sites, functional moieties responsible for channel activation and thus mechanism of action, have yet to be established. Here, we present a proof-of-principle study that combines de-novo drug design, molecular modeling, chemical synthesis with whole cell electrophysiology and Action Potential (AP) recordings in fetal mouse ventricular myocytes to establish basic chemical principles required for efficient activator of hERG1 channel. In order to minimize the likelihood that these molecules would also block the hERG1 channel they were computationally engineered to minimize interactions with known intra-cavitary drug binding sites. The combination of experimental and theoretical studies led to identification of functional elements (functional groups, flexibility) underlying efficiency of hERG1 activators targeting binding pocket located in the S4–S5 linker, as well as identified potential side-effects in this promising line of drugs, which was associated with multi-channel targeting of the developed drugs.     

Phytochrome A Function in Red Light Sensing

Light signals perceived by the phytochrome family of red (R) and far-red (FR) light-absorbing photoreceptors direct plant growth and development throughout their lifecycle. In contrast to other family members, phyA displays rapid light-induced proteolytic degradation upon conversion to the biologically active Pfr form and mediates high irradiance responses to continuous FR. These unique properties together with limited examples of phyA function in R have resulted in an over-simplified portrayal of phyA as a FR sensor which acts predominantly in seed germination and early stages of seedling de-etiolation. In a recent work, published in The Plant Journal, we report significant phyA activity in Arabidopsis thaliana at high (>100 µmolm⁻²s⁻¹) photon irradiances of R. Under these conditions, we observed retarded degradation of a pool of nuclear-localised phyA, consistent with the phenomenon of photoprotection, and showed phyBphyCphyDphyE quadruple null mutants, containing only functional phyA, to de-etiolate and survive to flowering. The photon irradiances used in this study were greater than those routinely used for photomorphogenic analysis in the laboratory but considerably lower than those commonly observed in daylight. In this addendum we present additional analyses of the phyBphyCphyDphyE mutant and discuss the possibility that phyA may perform a significant role in the growth and development of daylight-grown plants.Key Words: phytochrome A, red light, irradiance, hypocotyl, cotyledon, photoprotection     

Interactions of H562 in the S5 Helix with T618 and S621 in the Pore Helix Are Important Determinants of hERG1 Potassium Channel Structure and Function

hERG1 is a member of the cyclic nucleotide binding domain family of K⁺ channels. Alignment of cyclic nucleotide binding domain channels revealed an evolutionary conserved sequence HwX(A/G)C in the S5 domain. We reasoned that histidine 562 in hERG1 could play an important structure-function role. To explore this role, we created in silica models of the hERG1 pore domain based on the KvAP crystal structure with Rosetta-membrane modeling and molecular-dynamics simulations. Simulations indicate that the H562 residue in the S5 helix spans the gap between the S5 helix and the pore helix, stabilizing the pore domain, and that mutation at the H562 residue leads to a disruption of the hydrogen bonding to T618 and S621, resulting in distortion of the selectivity filter. Analysis of the simulated point mutations at positions 562/618/621 showed that the reciprocal double mutations H562W/T618I would partially restore the orientation of the 562 residue. Matching hydrophobic interactions between mutated W562 residue and I618 partially compensate for the disrupted hydrogen bonding. Complementary in vitro electrophysiological studies confirmed the results of the molecular-dynamics simulations on single mutations at positions 562, 618, and 621. Experimentally, mutations of the H562 to tryptophan produced a functional channel, but with slowed deactivation and shifted V_1/2 of activation. Furthermore, the double mutation T618I/H562W rescued the defects seen in activation, deactivation, and potassium selectivity seen with the H562W mutation. In conclusion, interactions between H562 in the S5 helix and amino acids in the pore helix are important determinants of hERG1 potassium channel function, as confirmed by theory and experiment.     

hERG1a N-terminal eag domain-containing polypeptides regulate homomeric hERG1b and heteromeric hERG1a/hERG1b channels: a possible mechanism for long QT syndrome

Human ether-á-go-go-related gene (hERG) potassium channels are critical for cardiac action potential repolarization. Cardiac hERG channels comprise two primary isoforms: hERG1a, which has a regulatory N-terminal Per-Arnt-Sim (PAS) domain, and hERG1b, which does not. Isolated, PAS-containing hERG1a N-terminal regions (NTRs) directly regulate NTR-deleted hERG1a channels; however, it is unclear whether hERG1b isoforms contain sufficient machinery to support regulation by hERG1a NTRs. To test this, we constructed a series of PAS domain-containing hERG1a NTRs (encoding amino acids 1-181, 1-228, 1-319, and 1-365). The NTRs were also predicted to form from truncation mutations that were linked to type 2 long QT syndrome (LQTS), a cardiac arrhythmia disorder associated with mutations in the hERG gene. All of the hERG1a NTRs markedly regulated heteromeric hERG1a/hERG1b channels and homomeric hERG1b channels by decreasing the magnitude of the current-voltage relationship and slowing the kinetics of channel closing (deactivation). In contrast, NTRs did not measurably regulate hERG1a channels. A short NTR (encoding amino acids 1-135) composed primarily of the PAS domain was sufficient to regulate hERG1b. These results suggest that isolated hERG1a NTRs directly interact with hERG1b subunits. Our results demonstrate that deactivation is faster in hERG1a/hERG1b channels compared to hERG1a channels because of fewer PAS domains, not because of an inhibitory effect of the unique hERG1b NTR. A decrease in outward current density of hERG1a/hERG1b channels by hERG1a NTRs may be a mechanism for LQTS.     

Function of Light in the Light-induced Geotropic Response in Zea Roots

The light doses just above the threshold energy value for inducing the geotropic responsiveness in the roots of Zea mays L., cv. Golden Cross Bantam 70, caused a drastic rise in the NADPH level and a drop in the NADP level in 2-millimeter root tips. Some reducing agents lowered the threshold energy value up to about one-third of the control. From these results, we deduce that light may exert two functions in the geotropic response of Zea primary roots, one being the photochemical transformation of a photoreceptor and the other being the induction of a reduction state in the tissue.     

植物SNARE蛋白的结构与功能

在真核生物细胞囊泡运输过程中的膜融合主要是由SNARE蛋白介导的,SNARE蛋白的结构高度保守.研究发现,植物中的SNARE蛋白促进植物细胞板形成,能与离子通道蛋白相互作用,有利于植物的正常生长发育,能提高植物的抗病性及参与植物的向重力性作用.应用基因组学和蛋白质组学技术结合细胞学水平上的分析方法有助于深入揭示植物SNARE蛋白家族成员的功能,明确SNARE蛋白在信号转导途径中的作用,阐明动植物免疫系统的区别和联系.     

Membrane Structure and Function

An understanding of the biochemical basis of membrane function is an important goal of present day biology. In this paper, a biochemical approach to the problem of the specific transport of sugars across the membrane of Escherichia coli is discussed. A new biochemical model for lactose transport system in this organism is presented, in which a specific membrane protein (M protein) plays the role of the sugar carrier. Experiments which have led to the discovery of such a protein, its specific labeling, and partial purification are briefly reviewed.     

结构函数的标度律

分析了GOY模型结构函数的标度律．指出结构函数的振荡涨落导致非线性标度律。     

膨胀素的结构与功能

膨胀素是植物细胞生长期间释放的一种能使细胞壁松弛的蛋白质,是细胞壁伸展的关键调节剂,对细胞生长有重要作用。膨胀素由庞大的基因家族编码,分为α-、β-、γ-和δ-膨胀素。膨胀素有多种功能,研究它对搞清生长机制有着重要的意义。