V1 Alyssia 声望 1 生理学与生物物理学 2024-03-28 21:10:16 上传
Solution structure of the rat P2X4 receptor head domain involved in inhibitory metal binding
Abstract The P2X receptor is an ATP-gated cation channel expressed on the plasma membrane. The head domain (Gln111–Val167 in the rat P2X4 receptor) regulates ATP-induced cation influx. In this study, we prepared a head domain with three disulfide bonds, such as the intact rat P2X4 receptor contains. NMR analysis showed that the head domain possessed the same fold as in the zebrafish P2X4 receptor previously determined by crystallography. Furthermore, the inhibitory, divalent, metal ion binding sites were determined by NMR techniques. These findings will be useful for the design of specific inhibitors for the P2X receptor family.
V1 高连仁 声望 1 动植物检疫 2024-03-28 15:50:25 上传
Dissecting the functional roles of the conserved NXXE and HXE motifs of the ADP-dependent glucokinase from Thermococcus litoralis
Abstract The activity of the ADP-dependent glucokinase from Thermococcus litoralis (TlGK) relies on the highly conserved motifs NXXE (i.e. Asn-Xaa-Xaa-Glu) and HXE (i.e. His-Xaa-Glu). Site-directed mutagenesis of residues Glu279 (HXE) and Glu308 (NXXE) leads to enzymes with highly reduced catalytic rates. The replacement of Glu308 by Gln increased the KM for MgADP− and was activated by free Mg2+. On the other hand, HXE mutants did not affect the KM for MgADP−, were still inhibited by free Mg2+, and caused a large increase on KM for glucose and an 87-fold weaker binding of glucose onto the non-hydrolysable TlGK·AMP–AlF3 complex. Our findings put forward the fundamental role of the HXE motif in glucose binding during ternary complex formation.
V1 阿随向前冲 声望 1 生物信息技术 2024-03-27 03:41:45 上传
Dynamics, flexibility, and allostery in molecular chaperonins
Abstract The chaperonins are a family of molecular chaperones present in all three kingdoms of life. They are classified into Group I and Group II. Group I consists of the bacterial variants (GroEL) and the eukaryotic ones from mitochondria and chloroplasts (Hsp60), while Group II consists of the archaeal (thermosomes) and eukaryotic cytosolic variants (CCT or TRiC). Both groups assemble into a dual ring structure, with each ring providing a protective folding chamber for nascent and denatured proteins. Their functional cycle is powered by ATP binding and hydrolysis, which drives a series of structural rearrangements that enable encapsulation and subsequent release of the substrate protein. Chaperonins have elaborate allosteric mechanisms to regulate their functional cycle. Long-range negative cooperativity between the two rings ensures alternation of the folding chambers. Positive intra-ring cooperativity, which facilitates concerted conformational transitions within the protein subunits of one ring, has only been demonstrated for Group I chaperonins. In this review, we describe our present understanding of the underlying mechanisms and the structure–function relationships in these complex protein systems with a particular focus on the structural dynamics, allostery, and associated conformational rearrangements.
V3 叶与秋 声望 59 生物技术 2024-03-26 18:46:49 上传
Reptin physically interacts with p65 and represses NF-κB activation
Abstract Reptin and Pontin belong to the AAA+ ATPase family of DNA helicases. Both proteins are present in several chromatin-remodeling machineries and are involved in transcriptional regulation, DNA repair, and telomerase activity, but they also function independently from each other. Here we report the identification of p65 as an interacting partner of Reptin. Using reporter gene assays, we show Reptin inhibits NF-κB transactivation after TNFα stimulation. Reptin is mainly localized in the cytoplasm and impedes NF-κB activation by inhibiting IκB-α degradation and restraining p65 nuclear translocation. These results reveal a novel mechanism for the control of NF-κB pathway by cytoplasmic Reptin.
V2 弗拉明哥 声望 11 生物科学 2024-03-23 12:37:02 上传
Insights into the behavioral difference of water in the presence of GM1
Abstract Studies on the structure and dynamics of interfacial water, emphasizing on the properties of water near the surface of biomolecules, are well reported, but there is a lack of evidence on the behavior of water near a comparatively rough surface containing molecules with a bulky head group like GM1. In this report we comparatively analyze the structure and dynamics of water as a function of distance from the lipid head group in GM1 containing lipid bilayers, with the lipid bilayers where GM1 is not present. This approach effectively demonstrates the behavioral difference and hence delayed convergence from bound water to bulk water in the presence of GM1 compared to a relatively smooth surface.
V1 北邮老土 声望 1 生物工程 2024-03-23 10:13:15 上传
Identification and evolution of the orphan genes in the domestic silkworm, Bombyx mori
Abstract Orphan genes (OGs) which have no recognizable homology to any sequences in other species could contribute to the species specific adaptations. In this study, we identified 738 OGs in the silkworm genome. About 31% of the silkworm OGs is derived from transposable elements, and 5.1% of the silkworm OGs emerged from gene duplication followed by divergence of paralogs. Five de novo silkworm OGs originated from non-coding regions. Microarray data suggested that most of the silkworm OGs were expressed in limited tissues. RNA interference experiments suggested that five de novo OGs are not essential to the silkworm, implying that they may contribute to genetic redundancy or species-specific adaptation. Our results provide some new insights into the evolutionary significance of the silkworm OGs.
V1 Anacletus 声望 1 动物资源科学 2024-03-23 04:33:03 上传
PKA-mediated phosphorylation of Dexras1 suppresses iron trafficking by inhibiting S-nitrosylation
Abstract Dexras1 is a small GTPase and plays a central role in neuronal iron trafficking. We have shown that stimulation of glutamate receptors activates neuronal nitric oxide synthase, leading to S-nitrosylation of Dexras1 and a physiological increase in iron uptake. Here we report that Dexras1 is phosphorylated by protein kinase A (PKA) on serine 253, leading to a suppression of iron influx. These effects were directly associated with the levels of S-nitrosylated Dexras1, whereby PKA activation reduced Dexras1 S-nitrosylation in a dose dependent manner. Moreover, we found that adiponectin modulates Dexras1 via PKA. Hence these findings suggest the involvement of the PKA pathway in modulating glutamate-mediated ROS in neurons, and hint to a functional crosstalk between S-nitrosylation and phosphorylation.
V2 弓谷所長 声望 7 生物信息学 2024-03-23 03:54:58 上传
Unusual effects of crowders on heme retention in myoglobin
Abstract Myoglobin (Mb) undergoes pronounced heme loss under denaturing conditions wherein the proximal histidine gets protonated. Our data show that macromolecular crowding agents (both synthetic and protein based) can appreciably influence the extent of heme retention in Mb. Interestingly, glucose and sucrose, the monomeric constituents of dextran and ficoll-based crowders were much more effective in preventing heme dissociation of Mb, albeit, at much higher concentrations. The protein crowders BSA and lysozyme show very interesting results with BSA bringing about the maximum heme retention amongst all the crowding agents used while lysozyme induced heme dissociation even in the native state of Mb. The stark difference that these protein crowders exhibit when interacting with the heme protein is a testament to the varied interaction potentials that a test protein might be exposed to in the physiological (crowded) milieu.
V1 bingo_ 声望 1 生物科学 2024-03-22 23:05:41 上传
Structure and intrinsic disorder of the proteins of the Trypanosoma brucei editosome
Abstract Mitochondrial pre-mRNAs in trypanosomatids undergo RNA editing to be converted into translatable mRNAs. The reaction is characterized by the insertion and deletion of uridine residues and is catalyzed by a macromolecular protein complex called the editosome. Despite intensive research, structural information for the majority of editosome proteins is still missing and no high resolution structure for the editosome exists. Here we present a comprehensive structural bioinformatics analysis of all proteins of the Trypanosoma brucei editosome. We specifically focus on the interplay between intrinsic order and disorder. According to computational predictions, editosome proteins involved in the basal reaction steps of the processing cycle are mostly ordered. By contrast, thirty percent of the amino acid content of the editosome is intrinsically disordered, which includes most prominently proteins with OB-fold domains. Based on the data we suggest a functional model, in which the structurally disordered domains of the complex are correlated with the RNA binding and RNA unfolding activity of the T. brucei editosome.
V2 黄绮娜 声望 1 生物化学与分子生物学 2024-03-22 17:51:36 上传
Human Mpn1 promotes post-transcriptional processing and stability of U6atac
Abstract Mpn1 is an exoribonuclease that modifies the spliceosomal small nuclear RNA (snRNA) U6 by trimming its oligouridine tail and introducing a cyclic phosphate group (>p). Mpn1 deficiency induces U6 3′ end misprocessing, accelerated U6 decay and pre-mRNA splicing defects. Mutations in the human MPN1 gene are associated with the genodermatosis Clericuzio-type poikiloderma with neutropenia (PN). Here we present the deep sequencing of the >p-containing transcriptomes of mpn1Δ fission yeast and PN cells. While in yeast U6 seems to be the only substrate of Mpn1, human Mpn1 also processes U6atac snRNA. PN cells bear unstable U6atac species with aberrantly long and oligoadenylated 3′ ends. Our data corroborate the link between Mpn1 and snRNA stability suggesting that PN could derive from pre-mRNA splicing aberrations.

生物化学是指用化学的方法和理论研究生命的化学分支学科。其任务主要是了解生物的化学组成、结构及生命过程中各种化学变化。从早期对生物总体组成的研究,进展到对各种组织和细胞成分的精确分析。目前正在运用诸如光谱分析、同位素标记、X射线衍射、电子显微镜以及其他物理学、化学技术,对重要的生物大分子(如蛋白质、核酸等)进行分析,以此说明这些生物大分子的多种多样的功能与它们特定的结构关系。