rongsheng jin free sample

Lam, K. H., Guo, Z., Krez, N., Matsui, T., Perry, K., Weisemann, J., Rummel, A., Bowen, M. E. & Jin, R. A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1. Nat Commun 9, 5367 (2018) doi: 10.1038/s41467-018-07789-4.

Chen, P., Tao, L., Liu, Z., Dong, M. & Jin, R. Structural insight into Wnt signaling inhibition by Clostridium difficile toxin B. FEBS J (2018) doi: 10.1111/febs.14681.

Chen, P., Tao, L., Wang, T., Zhang, J., He, A., Lam, K. H., Liu, Z., He, X., Perry, K., Dong, M*. & Jin, R*. Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B. Science 360, 664-669 (2018) (*corresponding authors) doi: 10.1126/science.aar1999. PMCID: PMC6231499

Lam, K. H., Sikorra, S., Weisemann, J., Maatsch, H., Perry, K., Rummel, A., Binz, T. & Jin, R. Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA. Pathog Dis 76 (2018) doi: 10.1093/femspd/fty044. PMCID: PMC5961070

Silva, D. A., Stewart, L., Lam, K. H., Jin, R. & Baker, D. Structures and disulfide cross-linking of de novo designed therapeutic mini-proteins. FEBS J 285, 1783-1785 (2018) doi: 10.1111/febs.14394. PMCID: PMC6001749

Lam, K. H., Qi, R., Liu, S., Kroh, A., Yao, G., Perry, K., Rummel, A. & Jin, R. The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein. Toxicon 147, 19-26 (2018) doi: 10.1016/j.toxicon.2017.10.012. PMCID: PMC5902665

Chevalier, A., Silva, D.A., Rocklin, G.J., Hicks, D.R., Vergara, R., Murapa, P., Bernard, S.M., Zhang, L., Lam, K.H., Yao, G., Bahl, C.D., Miyashita, S.I., Goreshnik, I., Fuller, J.T., Koday, M.T., Jenkins, C.M., Colvin, T., Carter, L., Bohn, A., Bryan, C.M., Fernández-Velasco, D.A., Stewart, L., Dong, M., Huang, X., Jin, R., Wilson, I.A., Fuller, D.H. & Baker, D. Massively parallel de novo protein design for targeted therapeutics. Nature 550(7674):74-79 (2017) doi: 10.1038/nature23912. PMCID: PMC5802399

Yao, G., Lam, K.H., Weisemann, J., Peng, L., Krez, N., Perry, K., Shoemaker, C.B., Dong, M., Rummel, A. & Jin, R. A camelid single-domain antibody neutralizes botulinum neurotoxin A by blocking host receptor binding. Sci Rep. 7;7(1):7438. (2017) doi: 10.1038/s41598-017-07457-5. PMCID: PMC5547058

Yao, G., Lam, K.H., Perry, K., Weisemann, J., Rummel, A. & Jin, R. Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H. Toxins (Basel) 9, 93 (2017) doi: 10.3390/toxins9030093. PMCID: PMC5371848

Yao, G., Zhang, S., Mahrhold, S., Lam, K. H., Stern, D., Bagramyan, K., Perry, K., Kalkum, M., Rummel, A.*, Dong, M.* & Jin, R.* N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A. Nat Struct Mol Biol 23 (7):656-662 (2016) (*corresponding authors) doi: 10.1038/nsmb.3245. PMCID: PMC5033645

Lee, K., Lam, K. H., Kruel, A. M., Mahrhold, S., Perry, K., Cheng, L. W., Rummel, A. & Jin, R. Inhibiting oral intoxication of botulinum neurotoxin A complex by carbohydrate receptor mimics. Toxicon 107, 43-49 (2015) doi: 10.1016/j.toxicon.2015.08.003. PMCID: PMC4658216

Lam, K.H. & Jin, R. Architecture of the botulinum neurotoxin complex: a molecular machine for protection and delivery. Current Opinion in Structural Biology 31:89-95 (2015) doi: 10.1016/j.sbi.2015.03.013. PMCID: PMC4476938

Lam, K.H., Yao, G. & Jin, R. Diverse binding modes, same goal: The receptor recognition mechanism of botulinum neurotoxin. Progress in Biophysics and Molecular Biology 117(2-3):225-31 (2015) doi: 10.1016/j.pbiomolbio.2015.02.004. PMCID: PMC4417461

Lam, T.I., Stanker, L.H., Lee, K., Jin, R. & Cheng, L.W. Translocation of botulinum neurotoxin serotype A and associated proteins across the intestinal epithelia. Cellular Microbiology 17(8):1133-1143 (2015) doi: 10.1111/cmi.12424. PMCID: PMC4610714

Matsui, T.*, Gu, S., Lam, K.H., Carter, L.G., Rummel, A., Mathews, II. & Jin, R.* Structural Basis of the pH-Dependent Assembly of a Botulinum Neurotoxin Complex. J. Mol. Biol. 426(22):3773-3782 (2014) doi: 10.1016/j.jmb.2014.09.009. (*corresponding authors) PMCID: PMC4252799

Lee, K., Zhong, X., Gu, S., Kruel, A.M., Dorner, M.B., Perry, K., Rummel, A., Dong, M. & Jin, R. Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex. Science 344(6190):1405-1410 (2014) doi: 10.1126/science.1253823. PMCID: PMC4164303

Lee, K., Lam, K.H., Kruel, A.M., Perry, K., Rummel, A. and Jin, R. High-resolution crystal structure of HA33 of botulinum neurotoxin type B progenitor toxin complex. Biochem. Biophys. Res. Commun. 446(2):568-573 (2014) doi: 10.1016/j.bbrc.2014.03.008. PMCID: PMC4020412

Yao, Y., Lee, K., Gu, S., Lam, K.H. & Jin, R. Botulinum Neurotoxin A Complex Recognizes Host Carbohydrates through Its Hemagglutinin Component, Toxins (Basel) 6(2):624-635 (2014) doi: 10.3390/toxins6020624. PMCID: PMC3942755

Lee, K., Gu, S., Jin, L., Le, T.T.N., Cheng, L.W., Strotmeier, J., Kruel, A.M., Yao, G., Perry, K., Rummel, A.* & Jin, R.* Structure of a Bimodular Botulinum Neurotoxin Complex Provides Insights into Its Oral Toxicity. PLoS Pathog. 9(10): e1003690 (2013) doi:10.1371/journal.ppat.1003690. (*corresponding authors) PMCID: PMC3795040

Zong, Y. and Jin, R. Structural mechanisms of the agrin-LRP4-MuSK signaling pathway in neuromuscular junction differentiation. Cell. Mol. Life Sci. 70(17):3077-88 (2013) doi: 10.1007/s00018-012-1209-9. PMCID: PMC4627850

Gu, S. and Jin, R. Assembly and function of the botulinum neurotoxin progenitor complex. Curr. Top. Microbiol. Immunol. 364:21-44 (2013) doi: 10.1007/978-3-642-33570-9_2. PMCID: PMC3875173

Gu, S., Rumpel, S., Zhou, J., Strotmeier, J., Bigalke, H., Perry, K., Shoemaker, C.B., Rummel, A. & Jin, R. Botulinum neurotoxin is shielded by NTNHA in an interlocked complex. Science 335(6071):977-81 (2012) doi: 10.1126/science.1214270. PMCID: PMC3545708

Zong, Y., Zhang, B., Gu, S., Lee, K., Zhou, J., Yao, G., Figueiredo, D., Perry, K., Mei, L.* & Jin, R.* Structural basis of neuron-specific regulation of postsynaptic differentiation. Gene & Development 26:247-258 (2012) doi: 10.1101/gad.180885.111. (*corresponding authors) PMCID: PMC3278892

Yao, G., Zong, Y., Gu, S., Zhou, J., Xu, H., Mathews, II. & Jin, R. Crystal structure of the glutamate receptor GluA1 amino-terminal domain. Biochem. J. 438(2):255-63 (2011) doi: 10.1042/BJ20110801. PMCID: PMC3296483

Strotmeier, J., Gu, S., Jutzi, S., Mahrhold, S., Zhou, J., Pich, A., Eichner, T., Bigalke, H., Rummel, A.*, Jin, R.* & Binz, T*. The biological activity of botulinum neurotoxin type C is dependent upon novel types of ganglioside binding sites. Mol. Microbiol. 81(1):143-56 (2011) doi: 10.1111/j.1365-2958.2011.07682.x. Epub 2011 Jun 2. (*corresponding authors)

Strotmeier, J., Lee, K., Völker, A.K., Mahrhold, S., Zong, Y., Zeiser, J., Zhou, J., Pich, A., Bigalke, H., Binz, T., Rummel, A.* & Jin, R.* Botulinum neurotoxin serotype D attacks neurons via two carbohydrate-binding sites in a ganglioside-dependent manner. Biochem. J. 431(2):207-16 (2010) (*corresponding authors)

Jin, R.*, Singh, S.K., Gu, S., Furukawa, H., Sobolevsky, A.I., Zhou, J., Jin, Y. & Gouaux E.* Crystal structure and association behavior of the GluR2 amino-terminal domain. EMBO J. 28(12):1812-23 (2009) (*corresponding authors) PMCID: PMC2699365

Kumar, J., Schuck. P., Jin, R. & Mayer, M.L. The N-terminal domain of GluR6-subtype glutamate receptor ion channels. Nat. Struct. Mol. Biol. 16(6):631-8 (2009) PMCID: PMC2729365

Jin, R., Rummel, A., Binz, T. & Brunger, A.T. Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity. Nature 444:1092-5 (2006)

Jin, R., Clark, S., Weeks, A.M., Dudman, J.T., Gouaux, E. & Partin, K.M. Mechanism of positive allosteric modulators acting on AMPA receptors. J. Neurosci. 25(39):9027-36 (2005)

Jin, R., Junutula, J.R., Matern, H.T., Ervin, K.E., Scheller, R.H. & Brunger, A.T. Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase. EMBO J. 24:2064-74 (2005)

Jin, R., Bank, T., Mayer, M. L., Traynelis, S. & Gouaux, E. Structural basis for partial agonist action at ionotropic glutamate receptors. Nat. Neurosci. 6(8):803-10 (2003)

Zheng Liu, Conceptualization, Investigation, Visualization, Writing - original draft,1 Sicai Zhang, Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing,2 Peng Chen, Conceptualization, Methodology,1 Songhai Tian, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing,2 Ji Zeng, Investigation, Resources,2 Kay Perry, Investigation,3 Min Dong, Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing,2 and Rongsheng Jin, Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing1

34. Chen P., Lam K. H., Liu Z., Mindlin F. A., Chen B., Gutierrez C. B., Huang L., Zhang Y., Hamza T., Feng H., Matsui T., Bowen M. E., Perry K., Jin R.,

Citation:Lee K, Gu S, Jin L, Le TTN, Cheng LW, Strotmeier J, et al. (2013) Structure of a Bimodular Botulinum Neurotoxin Complex Provides Insights into Its Oral Toxicity. PLoS Pathog 9(10):

20.Inoue K, Fujinaga Y, Watanabe T, Ohyama T, Takeshi K, et al. (1996) Molecular composition of Clostridium botulinum type A progenitor toxins. Infect Immun 64: 1589–1594.

25.Fujinaga Y, Inoue K, Nomura T, Sasaki J, Marvaud JC, et al. (2000) Identification and characterization of functional subunits of Clostridium botulinum type A progenitor toxin involved in binding to intestinal microvilli and erythrocytes. FEBS Lett 467: 179–183.

26.Inoue K, Fujinaga Y, Honke K, Arimitsu H, Mahmut N, et al. (2001) Clostridium botulinum type A haemagglutinin-positive progenitor toxin (HA(+)-PTX) binds to oligosaccharides containing Gal beta1-4GlcNAc through one subcomponent of haemagglutinin (HA1). Microbiology 147: 811–819.

27.Sugawara Y, Matsumura T, Takegahara Y, Jin Y, Tsukasaki Y, et al. (2010) Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin. J Cell Biol 189: 691–700.

28.Jin Y, Takegahara Y, Sugawara Y, Matsumura T, Fujinaga Y (2009) Disruption of the epithelial barrier by botulinum haemagglutinin (HA) proteins - differences in cell tropism and the mechanism of action between HA proteins of types A or B, and HA proteins of type C. Microbiology 155: 35–45.

29.Matsumura T, Jin Y, Kabumoto Y, Takegahara Y, Oguma K, et al. (2008) The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption. Cell Microbiol 10: 355–364.

32.Fujita R, Fujinaga Y, Inoue K, Nakajima H, Kumon H, et al. (1995) Molecular characterization of two forms of nontoxic-nonhemagglutinin components of Clostridium botulinum type A progenitor toxins. FEBS Lett 376: 41–44.

33.Ohyama T, Watanabe T, Fujinaga Y, Inoue K, Sunagawa H, et al. (1995) Characterization of nontoxic-nonhemagglutinin component of the two types of progenitor toxin (M and L) produced by Clostridium botulinum type D CB-16. Microbiol Immunol 39: 457–465.

We thank Robbin Newlin for assistance with tissue preparation and immunostaining. We thank Core H of the Consortium for Functional Glycomics (CFG) for glycan array screening. This work was partly supported by National Institute of Allergy and Infectious Diseases (NIAID) grant R01AI091823 to Rongsheng Jin.

16.Gu, S.; Rumpel, S.; Zhou, J.; Strotmeier, J.; Bigalke, H.; Perry, K.; Shoemaker, C.B.; Rummel, A.; Jin, R. Botulinum neurotoxin is shielded by NTNHA in an interlocked complex. Science 2012, 335, 977-981.

17.Lee, K.; Gu, S.; Jin, L.; Le, T.T.; Cheng, L.W.; Strotmeier, J.; Kruel, A.M.; Yao, G.; Perry, K.; et al. Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity. PLoSPathog. 2013, 9, e1003690.

18.Amatsu, S.; Sugawara, Y.; Matsumura, T.; Kitadokoro, K.; Fujinaga, Y. Crystal structure of Clostridium botulinum whole hemagglutinin reveals a huge triskelion-shaped molecular complex. J. Biol. Chem. 2013, 288, 35617-35625.

22.Fujinaga, Y.; Inoue, K.; Watanabe, S.; Yokota, K.; Hirai, Y.; Nagamachi, E.; Oguma, K. The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin. Microbiology 1997, 143, 3841-3847.

23.Nishikawa, A.; Uotsu, N.; Arimitsu, H.; Lee, J.C.; Miura, Y.; Fujinaga, Y.; Nakada, H.; Watanabe, T.; Ohyama, T.; Sakano, Y.; et al. The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cells. Biochem. Biophys. Res. Commun. 2004, 319, 327-333.

In biomedicine, human fibrinogen, hepatitis B surface antigen, human immuoglobulin G, and human serum albumin are often used as mode proteins. Using the aforementioned proteins as models with the biosensor, the feasibility is shown in Figure 4. Significant increases of gray-scale value appear in the square areas exposed to the corresponding target (Jin, et al., 2003). These results demonstrate that target samples can be identified by the ellipsometry-based biosensor.

Detection of several model proteins using the biosensor based on ellipsometry. Model proteins Fib, AntiHBsA, IgG and HSA were immobilized in four different columns, respectively. Phosphate-buffered saline was added to one area as a reference control. Corresponding target was then added to the other two areas in the column. (Z.H. Wang & Jin, 2003b)

Binding curves of anti-fibrinogen/fibrinogen (■), anti-human immunoglobulin/human immunoglobulin (●), and anti-human serum albumin/human serum albumin (▲) obtained by the biosensor (Z.H. Wang & Jin, 2003b).

Analyzing only one tumor marker is insufficient to diagnose cancer in 2010, a review exhibited a novel co-detection of three common tumor markers: alpha-fetoprotein, alpha-L-fucosidase, and ferritin (Jin, 2011). Thus, quantitative analysis was performed by the biosensor with the following calibration curve method:

Hepatitis B virus infection is the most common cause of chronic liver diseases; an estimated 350 million people are chronically infected with hepatitis B virus worldwide (Sun, et al., 2002). Further, hepatitis B virus infection plays an important role in the development of hepatocellular carcinoma (De Mitri, et al., 2010). A rapid, simple, and direct method is urgently needed for clinical hepatitis B diagnosis. In section 3.2.1, the screening probe, standard national reference sample detection, and highly sensitive hepatitis B detection results demonstrated that the biosensor based on ellipsometry is feasible for clinical diagnosis of the disease (Z.H. Wang, et al., 2006; Jin, et al., 2004). Thus, the application of the biosensor based on ellipsometry could greatly enhance hepatitis B detection speed.

Sera from 169 patients were analyzed with the biosensor for the purpose of clinical diagnosis. Samples from 60 patients included clinical information of hepatitis B from Shandong Provincial Hospital from qualitative enzyme-linked immunosorbent assay detection results (the assay kit was produced by Shanghai Rongsheng Biotech Co. Ltd). The remaining samples were from patients from the Tientsin Blood Disease Hospital and also included clinical information of hepatitis B (the assay kit was produced by Beijing Wantai Co Ltd.) Figure 11 shows the detection results of 109 hepatitis B patients’ sera samples from

Membrane-associated proteins provide the minimal fusion machinery necessary for cellular vesicles to fuse to target organelle membranes in eukaryotic cells (Jahn & Scheller, 2006). The qualitative and quantitative identification of membrane-associated proteins interactions is the key to understanding the mechanisms of membrane fusion, which is vital for cell division, cellular structure organization, and biological information processing (Zhang, et al., 2009). To investigate the characteristics of these newly discovered membrane-associated protein pairs such as: Sec22, Ykt6, Sso2 and Sso1, the biosensor based on ellipsometry was used to detect the interactions among soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs, a kind of protein that assembles into coiled-coil tetramers to promote membrane fusion). The interactions among several SNAREs (i.e., Sec22, Ykt6, Sso1, and Sso2) were analyzed by the biosensor based on ellipsometry. The in vitro detection results from the biosensor are consistent with the results of yeast two-hybrid assays at the domain level in vivo (Zhang, et al., 2009; Jin et al., 2011). Further, the kinetic binding process of two SNAREs (Ykt6 and Sso2) was measured using the real-time function of the biosensor. The rapid detection and identification of vesicular protein–protein interactions is essential for understanding vesicle trafficking and for understanding the system-level organization of cellular structure, biological information processing, and molecular mechanisms.

Recently, a type of total internal reflection imaging ellipsometry was developed for real-time detection of biomolecular interactions (Jin, et al., 2011). This method was used to visualization the of vesicles adsorption process. Non-specific adsorption and desorption on a poly-L-lysine-modified gold surface was analyzed with real-time curves by the biosensor. The biosensor results were consistent with a phase contrast microscopy (NIKON, TI-U, Japan) results. The vesicle adsorption and desorption processes visualized by the biosensor are significant to the study of cell membrane properties. Micron target detection is the future aim of the biosensor based on total internal reflection imaging ellipsometry. Therefore, we expect that the biosensor based on ellipsometry has a yet-unexploited huge market potential for application in biological basic research related to the health field.