2013 Vol. 4, No. 8

Ging-Hsi Wong and Chinese physiopsychology
Shu Zheng
2013, 4(8): 563-564. doi: 10.1007/s13238-013-3803-5
The NLRP3 Inflammasome activation in human or mouse cells, sensitivity causes puzzle
Hongbin Wang, Liming Mao, Guangxun Meng
2013, 4(8): 565-568. doi: 10.1007/s13238-013-3905-0
The sequence signature of an Ig-fold
Jia-Huai Wang
2013, 4(8): 569-572. doi: 10.1007/s13238-013-3903-2
Ig superfamily (IgSF) constitutes the largest superfamily in human genome. In particular, Ig-like domains are the most abundant structural module within cell surface receptors, functioning in nervous as well as immune system. Here I describe some key sequence signature of an I-set Ig-like domain from known structures of IgSF members. These signature residues define the I-set Ig-like domain, which should aid structural and functional studies of cell surface receptors.
How will telomeric complex be further contributed to our longevity?—The potential novel biomarkers of telomere complex counteracting both aging and cancer
Yiming Lu, Bohua Wei, Tao Zhang, Zi Chen, Jing Ye
2013, 4(8): 573-581. doi: 10.1007/s13238-013-3002-4
With the smooth move towards the coming expected clinical reports of anticancer pharmaceutical molecules targeting telomeres and telomerase, and also with the exciting success in the extension of lifespan by regulating telomerase activity without increased onset of oncogenesis in laboratory mouse models (Garcia-Cao et al., 2006; Jaskelioff et al., 2011), we are convinced that targeting telomeres based on telomerase will be a potential approach to conquer both aging and cancer and the idea of longevity seems to be no more mysterious. More interestingly, emerging evidences from clinical research reveal that other telomeric factors, like specific telomeric binding proteins and nonspecific telomere associated proteins also show crucial importance in aging and oncogenesis. This stems from their roles in the stability of telomere structure and in the inhibition of DNA damage response at telomeres. Uncapping these proteins from chromosome ends leads to dramatic telomere loss and telomere dysfunction which is more abrupt than those induced by telomerase inactivation. Abnormal expression of these factors results in developmental failure, aging and even oncogenesis evidenced by several experimental models and clinical cases, indicating telomere specific proteins and its associated proteins have complimentary roles to telomerase in telomere protection and controlling cellular fate. Thus, these telomeric factors might be potential clinical biomarkers for early detection or even therapeutic targets of aging and cancer. Future studies to elucidate how these proteins function in telomere protection might benefit patients suffering aging or cancer who are not sensitive to telomerase mediation.
Respiratory supercomplexes: structure, function and assembly
Rasika Vartak, Christina Ann-Marie Porras, Yidong Bai
2013, 4(8): 582-590. doi: 10.1007/s13238-013-3032-y
The mitochondrial respiratory chain consists of 5 enzyme complexes that are responsible for ATP generation. The paradigm of the electron transport chain as discrete enzymes diffused in the inner mitochondrial membrane has been replaced by the solid state supercomplex model wherein the respiratory complexes associate with each other to form supramolecular complexes. Defects in these supercomplexes, which have been shown to be functionally active and required for forming stable respiratory complexes, have been associated with many genetic and neurodegenerative disorders demonstrating their biomedical significance. In this review, we will summarize the functional and structural significance of supercomplexes and provide a comprehensive review of their assembly and the assembly factors currently known to play a role in this process.
YB-1 stabilizes HIV-1 genomic RNA and enhances viral production
Xin Mu, Wei Li, Xinlu Wang, Guangxia Gao
2013, 4(8): 591-597. doi: 10.1007/s13238-013-3011-3
HIV-1 utilizes cellular factors for efficient replication. The viral RNA is different from cellular mRNAs in many aspects, and is prone to attacks by cellular RNA quality control systems. To establish effective infection, the virus has evolved multiple mechanisms to protect its RNA. Here, we show that expression of the Y-box binding protein 1 (YB-1) enhanced the production of HIV-1. Downregulation of endogenous YB-1 in producer cells decreased viral production. YB-1 increased viral protein expression by stabilizing HIV-1 RNAs. The stem loop 2 in the HIV-1 RNA packaging signal was mapped to be the YB-1-responsive element. Taken together, these results indicate that YB-1 stabilizes HIV-1 genomic RNA and thereby enhances HIV-1 gene expression and viral production.
Research article
Ultrafast, accurate, and robust localization of anisotropic dipoles
Yongdeng Zhang, Lusheng Gu, Hao Chang, Wei Ji, Yan Chen, Mingshu Zhang, Lu Yang, Bei Liu, Liangyi Chen, Tao Xu
2013, 4(8): 598-606. doi: 10.1007/s13238-013-3904-1
The resolution of single molecule localization imaging techniques largely depends on the precision of localization algorithms. However, the commonly used Gaussian function is not appropriate for anisotropic dipoles because it is not the true point spread function. We derived the theoretical point spread function of tilted dipoles with restricted mobility and developed an algorithm based on an artificial neural network for estimating the localization, orientation and mobility of individual dipoles. Compared with fitting-based methods, our algorithm demonstrated ultrafast speed and higher accuracy, reduced sensitivity to defocusing, strong robustness and adaptability, making it an optimal choice for both two-dimensional and threedimensional super-resolution imaging analysis.
Structure of the catalytic domain of a state transition kinase homolog from Micromonas algae
Jiangtao Guo, Xuepeng Wei, Mei Li, Xiaowei Pan, Wenrui Chang, Zhenfeng Liu
2013, 4(8): 607-619. doi: 10.1007/s13238-013-3034-9
Under natural environments, plants and algae have evolved various photosynthetic acclimation mechanisms in response to the constantly changing light conditions. The state transition and long-term response processes in photosynthetic acclimation involve remodeling and composition alteration of thylakoid membrane. A chloroplast protein kinase named Stt7/STN7 has been found to have pivotal roles in both state transition and longterm response. Here we report the crystal structures of the kinase domain of a putative Stt7/STN7 homolog from Micromonas sp. RCC299 (MsStt7d) in the apo form and in complex with various nucleotide substrates. MsStt7d adopts a canonical protein kinase fold and contains all the essential residues at the active site. A novel hairpin motif, found to be a conserved feature of the Stt7/STN7 family and indispensable for the kinase stability, interacts with the activation loop and fixes it in an active conformation. We have also demonstrated that MsStt7d is a dualspecificity kinase that phosphorylates both Thr and Tyr residues. Moreover, preliminary in vitro data suggest that it might be capable of phosphorylating a consensus N-terminal pentapeptide of light-harvesting proteins Micromonas Lhcp4 and Arabidopsis Lhcb1 directly. The potential peptide/protein substrate binding site is predicted based on the location of a pseudo-substrate contributed by the adjacent molecule within the crystallographic dimer. The structural and biochemical data presented here provide a framework for an improved understanding on the role of Stt7/STN7 in photosynthetic acclimation.
Vitamin C induces periodontal ligament progenitor cell differentiation via activation of ERK pathway mediated by PELP1
Yan Yan, Wenfeng Zeng, Shujun Song, Fayun Zhang, Wenxi He, Wei Liang, Zhongying Niu
2013, 4(8): 620-627. doi: 10.1007/s13238-013-3030-0
The differentiation of periodontal ligament (PDL) progenitor cells is important for maintaining the homeostasis of PDL tissue and alveolar bone. Vitamin C (VC), a water-soluble nutrient that cannot be biosynthesized by humans, is vital for mesenchymal stem cells differentiation and plays an important role in bone remodeling. Therefore, the objective of this study was to determine the function and mechanism of VC in PDL progenitor cells osteogenic differentiation at the molecular level. We demonstrated that VC could induce the osteogenic differentiation and maturation of PDL progenitor cell without other osteogenic agents. During the process, VC preferentially activated ERK1/2 but did not affect JNK or p38. Co-treatment with ERK inhibitor effectively decreased the Vitamin C-induced expression of Runx2. ERK inhibitor also abrogated Vitamin C-induced the minimized nodules formation. PELP1, a nuclear receptor co-regulator, was up-regulated under VC treatment. PELP1 knockdown inhibited ERK phosphorylation. The overexpression of PELP1 had a positive relationship with Runx2 expression. Taken together, we could make a conclude that VC induces the osteogenic differentiation of PDL progenitor cells via PELP1-ERK axis. Our finding implies that VC may have a potential in the regeneration medicine and application to periodontitis treatment.
Structure analysis of the extracellular domain reveals disulfide bond forming-protein properties of Mycobacterium tuberculosis Rv2969c
Lu Wang, Jun Li, Xiangxi Wang, Wu Liu, Xuejun C. Zhang, Xuemei Li, Zihe Rao
2013, 4(8): 628-640. doi: 10.1007/s13238-013-3033-x
Disulfide bond-forming (Dsb) protein is a bacterial periplasmic protein that is essential for the correct folding and disulfide bond formation of secreted or cell wallassociated proteins. DsbA introduces disulfide bonds into folding proteins, and is re-oxidized through interaction with its redox partner DsbB. Mycobacterium tuberculosis, a Gram-positive bacterium, expresses a DsbA-like protein (Rv2969c), an extracellular protein that has its Nterminus anchored in the cell membrane. Since Rv2969c is an essential gene, crucial for disulfide bond formation, research of DsbA may provide a target of a new class of anti-bacterial drugs for treatment of M.tuberculosis infection. In the present work, the crystal structures of the extracellular region of Rv2969c (Mtb DsbA) were determined in both its reduced and oxidized states. The overall structure of Mtb DsbA can be divided into two domains:a classical thioredoxin-like domain with a typical CXXC active site, and an α-helical domain. It largely resembles its Escherichia coli homologue EcDsbA, however, it possesses a truncated binding groove; in addition, its active site is surrounded by an acidic, rather than hydrophobic surface. In our oxidoreductase activity assay, Mtb DsbA exhibited a different substrate specificity when compared to EcDsbA. Moreover, structural analysis revealed a second disulfide bond in Mtb DsbA, which is rare in the previously reported DsbA structures, and is assumed to contribute to the overall stability of Mtb DsbA. To investigate the disulphide formation pathway in M.tuberculosis, we modeled Mtb Vitamin K epoxide reductase (Mtb VKOR), a binding partner of Mtb DsbA, to Mtb DsbA.
Inactivation of Cdc42 in embryonic brain results in hydrocephalus with ependymal cell defects in mice
Xu Peng, Qiong Lin, Yang Liu, Yixin Jin, Joseph E. Druso, Marc A. Antonyak, Jun-Lin Guan, Richard A. Cerione
2013, 4(8): 641-641. doi: 10.1007/s13238-013-0804-3