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1.
Jing Su Yang Li Neil Shaw Weihong Zhou Min Zhang Hao Xu Bi-Cheng Wang Zhi-Jie Liu 《蛋白质与细胞》2010,1(5):453
Sometimes crystals cannot diffract X-rays beyond 3.0 ? resolution due to the intrinsic flexibility associated with the protein. Low resolution diffraction data not only pose a challenge to structure determination, but also hamper interpretation of mechanistic details. Crystals of a 25.6 kDa non-Pfam, hypothetical protein, PF2046, diffracted X-rays to 3.38 ? resolution. A combination of Se-Met derived heavy atom positions with multiple cycles of B-factor sharpening, multi-crystal averaging, restrained refinement followed by manual inspection of electron density and model building resulted in a final model with a R value of 23.5 (Rfree=24.7). The asymmetric unit was large and consisted of six molecules arranged as a homodimer of trimers. Analysis of the structure revealed the presence of a RNA binding domain suggesting a role for PF2046 in the processing of nucleic acids. 相似文献
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AbstractIncreasing evidence shows that the formation of misfolded aggregates amyloid-β (Aβ) peptide is associated with the Alzheimer’s disease (AD). Recent experiments reveal a significant correlation of the amount of trimer species bound to neurons with increasing neuro-toxicity. Our previous computational study demonstrated that carbon nanotubes (CNT) can inhibit effectively the formation of β-sheet-rich oligomers of Aβ(16-22) – a hydrophobic peptide essential for Aβ fibrillization. However, the influence of CNT on the oligomers formed by full-length Aβ remains elusive. In this study, we have investigated the conformational dynamics of Aβ(1-42) trimer, built from an NMR structure of α-helical monomer, in the absence and presence of a single-walled carbon nanotube (SWCNT). Our simulations demonstrate that SWCNT can significantly hinder the trimerisation and prevents the secondary structure formation of Aβ(1-42) peptide. Hydrophobic and aromatic stacking interactions between SWCNT and Aβ play important roles in the secondary structure formation of the Aβ trimer. This study reveals a complete picture of the detailed preventable mechanism of full-length Aβ(1-42) by SWCNT, providing theoretical insights into the development of drug candidates of AD. 相似文献
3.
Wu SR Sjöberg M Wallin M Lindqvist B Ekström M Hebert H Koeck PJ Garoff H 《The EMBO journal》2008,27(20):2799-2808
The activity of the membrane fusion protein Env of Moloney mouse leukaemia virus is controlled by isomerization of the disulphide that couples its transmembrane (TM) and surface (SU) subunits. We have arrested Env activation at a stage prior to isomerization by alkylating the active thiol in SU and compared the structure of isomerization-arrested Env with that of native Env. Env trimers of respective form were isolated from solubilized particles by sedimentation and their structures were reconstructed from electron microscopic images of both vitrified and negatively stained samples. We found that the protomeric unit of both trimers formed three protrusions, a top, middle and a lower one. The atomic structure of the receptor-binding domain of SU fitted into the upper protrusion. This was formed similar to a bent finger. Significantly, in native Env the tips of the fingers were directed against each other enclosing a cavity below, whereas they had turned outward in isomerization-arrested Env transforming the cavity into an open well. This might subsequently guide the fusion peptides in extended TM subunits into the target membrane. 相似文献
4.
《Biotechnology and bioengineering》2018,115(4):885-899
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6.
Xiangqing Ding Kangli Cao Jing Wang Yanmin Wan Qinyun Chen Yanqin Ren Yongtang Zheng Mingzhao Zhu Renrong Tian Wenjun Wang Chen Zhao Xiaoyan Zhang Jianqing Xu 《中国病毒学》2021,36(4):784-795
Raising a heterologous tier 2 neutralizing antibody (nAb) response remains a daunting task for HIV vaccine development. In this study, we explored the utility of diverse HIV-1 envelope (Env) immunogens in a sequential immunization scheme as a solution to this task. This exploration stemmed from the rationale that gp145, a membrane-bound truncation form of HIV Env, may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode. We first showed that gp140 DNA prime-gp145 Tiantan vaccinia (TV) boost likely represents a general format for inducing potent nAb response in mice. However, when examined in rhesus macaque, this modality showed little effectiveness. To improve the efficacy, we extended the original modality by adding a strong protein boost, namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle (NP), which was generated by a newly developed click approach. The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule. Importantly, the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge. Collectively, our studies highlighted that diversification of Env immunogens, in both types and formulations, under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development. 相似文献
7.
Allophycocyanin: trimers,monomers, subunits,and homodimers 总被引:1,自引:0,他引:1
Allophycocyanin is a photosynthetic light-harvesting pigment-protein complex located in the phycobilisomes of cyanobacteria and red algae. Using dynamic light scattering and circular dichroism, solutions of purified allophycocyanin were shown to consist of homogeneous trimers (alpha3beta3) with a nonspherical shape over a very wide range of protein concentrations at pH 6.0 and 20 degrees C. Deconvolutions of the visible circular dichroism spectrum of the trimer were carried out for the first determination of the individual spectra of all six-component chromophores. The chromophores were shown to be in different microenvironments that helped determine the spectrum of the trimer. Monomers (alpha beta) that were formed in either the presence of 0.50M NaSCN or at 45 degrees C were shown to be completely reversible to trimers. However, subunits (alpha and beta) that were formed in either the presence of 8M urea or at 60 degrees C, using spectroscopy and gel-filtration column chromatography, were observed to only partially reconstitute trimers. Homodimers (alpha2 and/or beta2) formed during the regeneration of trimers. The homodimer, which was detected for the first time when both subunits were present, was shown to be in equilibrium with its subunits. Unlike the trimer situation, subunits were found to fully reconstitute monomers in the presence of 0.50M NaSCN. These results suggest a route to trimer assembly from subunits with monomers serving as intermediaries and the homodimers forming in a nonproductive step that did not interfere with the overall assembly scheme. 相似文献
8.
Crosby IT Bourke DG Jones ED Jeynes TP Cox S Coates JA Robertson AD 《Bioorganic & medicinal chemistry letters》2011,21(6):1644-1648
The discovery of a small molecule non-nucleoside inhibitor of Hepatitis B Virus is described. During our work on conocurvone derived naphthoquinone ‘trimers’ for the treatment of HIV, we discovered a potent inhibitor 9 of Hepatitis B Virus in an antiviral screen. During attempts to resynthesis 9 for proof of concept studies, we altered the synthesis in order to attempt to reduced side reactions and difficult to remove by-products. As a result we discovered a small molecule 19 that also was a potent inhibitor of HBV. Importantly, this small molecule inhibitor of Hepatitis B Virus is also an inhibitor of Hepatitis B Virus resistant to 3TC, a bench mark of nucleoside analogues active in the treatment of Hepatitis B Virus. The development of 19 as an agent to treat HBV infections is discussed. 相似文献
9.
Abstract Two RNA sequences, AAA and AUG, were studied by the conformational search program CICADA and by molecular dynamics (MD) in the framework of the AMBER force field, and also via thorough PDB database search. CICADA was used to provide detailed information about conformers and conformational interconversions on the energy surfaces of the above molecules. Several conformational families were found for both sequences. Analysis of the results shows differences, especially between the energy of the single families, and also in flexibility and concerted conformational movement. Therefore, several MD trajectories (altogether 16 ns) were run to obtain more details about both the stability of conformers belonging to different conformational families and about the dynamics of the two systems. Results show that the trajectories strongly depend on the starting structure. When the MD start from the global minimum found by CICADA, they provide a stable run, while MD starting from another conformational family generates a trajectory where several different conformational families are visited. The results obtained by theoretical methods are compared with the thorough database search data. It is concluded that all except for the highest energy conformational families found in theoretical result also appear in experimental data. Registry numbers: adenylyl-(3′ →5′)-adenylyl-(3′ →5′)-adenosine [917-44-2] adenylyl-(3′ →5′)-uridylyl-(3′ →5′)-guanosine [3494-35-7] 相似文献
10.
A. M. Bald L. A. Pieters V. Wray H. Kolodziej D. A. Vanden Berghe M. Claeys A. J. Vlietinck 《Phytochemistry》1991,30(12):4129-4135
Pavetannin A-2, a new A-type proanthocyanidin, along with the trimers cinnamtannin B-1, pavetannin B-1, B-2, B-3, B-5 and B-6 have been isolated in their free phenolic form from the stem bark of Pavetta owariensis. Spectral data and partial acid-catalysed degradation established their structures as ent-epicatechin-(4→8,2→O→7)-catechin, epicatechin-(4β→8,2β→O→7)-epicatechin-(4→8)-epicatechin, epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→8)-ent-epicatechin, epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→8)-epicatechin, epicatechin-(4β→6,2β→O→7)-epicatechin-(4β→8)-epicatechin, epicatechin-(4β→6,2β→O→7)-catechin-(4β→8)-epicatechin, epicatechin-(4β→8,2β→O→7)-epicatechin-(4→8)-catechin, respectively. 相似文献