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2. Trapping the HIV-1 V3 loop in a helical conformation enables broad neutralization

Author

Glögl, Matthias, Friedrich, Nikolas, Cerutti, Gabriele, Lemmin, Thomas, Kwon, Young D., Gorman, Jason, Maliqi, Liridona, Mittl, Peer R. E., Hesselman, Maria C., Schmidt, Daniel, Weber, Jacqueline, Foulkes, Caio, Dingens, Adam S., Bylund, Tatsiana, Olia, Adam S., Verardi, Raffaello, Reinberg, Thomas, Baumann, Nicolas S., Rusert, Peter, Dreier, Birgit, Shapiro, Lawrence, Kwong, Peter D., Plückthun, Andreas, and Trkola, Alexandra

Published
2023
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3. Robust Prediction of Relative Binding Energies for Protein–Protein Complex Mutations Using Free Energy Perturbation Calculations

Author

Sampson, Jared M., Cannon, Daniel A., Duan, Jianxin, Epstein, Jordan C.K., Sergeeva, Alina P., Katsamba, Phinikoula S., Mannepalli, Seetha M., Bahna, Fabiana A., Adihou, Hélène, Guéret, Stéphanie M., Gopalakrishnan, Ranganath, Geschwindner, Stefan, Rees, D. Gareth, Sigurdardottir, Anna, Wilkinson, Trevor, Dodd, Roger B., De Maria, Leonardo, Mobarec, Juan Carlos, Shapiro, Lawrence, Honig, Barry, Buchanan, Andrew, Friesner, Richard A., and Wang, Lingle

Published
2024
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5. A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins

Author

Chonira, Vikas, Kwon, Young D., Gorman, Jason, Case, James Brett, Ku, Zhiqiang, Simeon, Rudo, Casner, Ryan G., Harris, Darcy R., Olia, Adam S., Stephens, Tyler, Shapiro, Lawrence, Bender, Michael F., Boyd, Hannah, Teng, I-Ting, Tsybovsky, Yaroslav, Krammer, Florian, Zhang, Ningyan, Diamond, Michael S., Kwong, Peter D., An, Zhiqiang, and Chen, Zhilei

Published
2023
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7. Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking

Author

Liu, Lihong, Casner, Ryan G., Guo, Yicheng, Wang, Qian, Iketani, Sho, Chan, Jasper Fuk-Woo., Yu, Jian, Dadonaite, Bernadeta, Nair, Manoj S., Mohri, Hiroshi, Reddem, Eswar R., Yuan, Shuofeng, Poon, Vincent Kwok-Man, Chan, Chris Chung-Sing, Yuen, Kwok-Yung, Sheng, Zizhang, Huang, Yaoxing, Bloom, Jesse D., Shapiro, Lawrence, and Ho, David D.

Published
2023
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8. HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide

Author

Wang, Shuishu, Matassoli, Flavio, Zhang, Baoshan, Liu, Tracy, Shen, Chen-Hsiang, Bylund, Tatsiana, Johnston, Timothy, Henry, Amy R., Teng, I-Ting, Tripathi, Prabhanshu, Becker, Jordan E., Changela, Anita, Chaudhary, Ridhi, Cheng, Cheng, Gaudinski, Martin, Gorman, Jason, Harris, Darcy R., Lee, Myungjin, Morano, Nicholas C., Novik, Laura, O’Dell, Sijy, Olia, Adam S., Parchment, Danealle K., Rawi, Reda, Roberts-Torres, Jesmine, Stephens, Tyler, Tsybovsky, Yaroslav, Wang, Danyi, Van Wazer, David J., Zhou, Tongqing, Doria-Rose, Nicole A., Koup, Richard A., Shapiro, Lawrence, Douek, Daniel C., McDermott, Adrian B., and Kwong, Peter D.

Published
2023
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9. Vaccine elicitation and structural basis for antibody protection against alphaviruses

Author

Sutton, Matthew S., Pletnev, Sergei, Callahan, Victoria, Ko, Sungyoul, Tsybovsky, Yaroslav, Bylund, Tatsiana, Casner, Ryan G., Cerutti, Gabriele, Gardner, Christina L., Guirguis, Veronica, Verardi, Raffaello, Zhang, Baoshan, Ambrozak, David, Beddall, Margaret, Lei, Hong, Yang, Eun Sung, Liu, Tracy, Henry, Amy R., Rawi, Reda, Schön, Arne, Schramm, Chaim A., Shen, Chen-Hsiang, Shi, Wei, Stephens, Tyler, Yang, Yongping, Florez, Maria Burgos, Ledgerwood, Julie E., Burke, Crystal W., Shapiro, Lawrence, Fox, Julie M., Kwong, Peter D., and Roederer, Mario

Published
2023
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10. Rethinking the Unity of Science Hypothesis: Levels, Mechanisms, and Realization

Author

Shapiro, Lawrence, Shenker, Orly, Series Editor, Boneh, Nora, Series Editor, Lamm, Ehud, Editorial Board Member, Leicht, Reimund, Editorial Board Member, Harman, Oren, Editorial Board Member, Corry, Leo, Editorial Board Member, Hemmo, Meir, Editorial Board Member, Belkind, Ori, Editorial Board Member, Katzir, Shaul, Editorial Board Member, Hon, Giora, Editorial Board Member, Fisch, Menachem, Editorial Board Member, Ben-Menahem, Yemima, Editorial Board Member, Posy, Carl, Editorial Board Member, Levy, Arnon, Editorial Board Member, Shagrir, Oron, Editorial Board Member, Shavit, Ayelet, Editorial Board Member, Miller, Boaz, Editorial Board Member, Dolev, Yuval, Editorial Board Member, Chen-Morris, Raz, Editorial Board Member, Even-Ezra, Ayelet, Editorial Board Member, Gissis, Snait, Editorial Board Member, Ioannidis, Stavros, editor, and Vishne, Gal, editor

Published
2022
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13. Co-immunization with hemagglutinin stem immunogens elicits cross-group neutralizing antibodies and broad protection against influenza A viruses

Author

Moin, Syed M., Boyington, Jeffrey C., Boyoglu-Barnum, Seyhan, Gillespie, Rebecca A., Cerutti, Gabriele, Cheung, Crystal Sao-Fong, Cagigi, Alberto, Gallagher, John R., Brand, Joshua, Prabhakaran, Madhu, Tsybovsky, Yaroslav, Stephens, Tyler, Fisher, Brian E., Creanga, Adrian, Ataca, Sila, Rawi, Reda, Corbett, Kizzmekia S., Crank, Michelle C., Karlsson Hedestam, Gunilla B., Gorman, Jason, McDermott, Adrian B., Harris, Audray K., Zhou, Tongqing, Kwong, Peter D., Shapiro, Lawrence, Mascola, John R., Graham, Barney S., and Kanekiyo, Masaru

Published
2022
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15. Vaccine-induced human monoclonal antibodies to PfRH5 show broadly neutralizing activity againstP. falciparumclinical isolates

Author

Thiam, Laty Gaye, primary, McHugh, Kirsty, additional, Ba, Aboubacar, additional, Li, Rebecca, additional, Guo, Yicheng, additional, Pouye, Mariama N., additional, Cisse, Awa, additional, Pipini, Dimitra, additional, Diallo, Fatoumata, additional, Sene, Seynabou D., additional, Patel, Saurabh D., additional, Thiam, Alassane, additional, Sadio, Bacary D., additional, Mbengue, Alassane, additional, Vigan-Womas, Ines, additional, Sheng, Zizhang, additional, Shapiro, Lawrence, additional, Draper, Simon J., additional, and Bei, Amy K., additional

Published
2024
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16. Robust prediction of relative binding energies for protein-protein complex mutations using free energy perturbation calculations

Author

Sampson, Jared M., primary, Cannon, Daniel A., additional, Duan, Jianxin, additional, Epstein, Jordan C. K., additional, Sergeeva, Alina P., additional, Katsamba, Phinikoula S., additional, Mannepalli, Seetha M., additional, Bahna, Fabiana A., additional, Adihou, Hélène, additional, Guéret, Stéphanie M., additional, Gopalakrishnan, Ranganath, additional, Geschwindner, Stefan, additional, Rees, D. Gareth, additional, Sigurdardottir, Anna, additional, Wilkinson, Trevor, additional, Dodd, Roger B., additional, De Maria, Leonardo, additional, Mobarec, Juan Carlos, additional, Shapiro, Lawrence, additional, Honig, Barry, additional, Buchanan, Andrew, additional, Friesner, Richard A., additional, and Wang, Lingle, additional

Published
2024
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17. Cisinhibition of co-expressed DIPs and Dprs shapes neural development

Author

Morano, Nicholas C., primary, Lopez, Davys H., additional, Meltzer, Hagar, additional, Sergeeva, Alina P., additional, Katsamba, Phinikoula S., additional, Gupta, Himanshu Pawankumar, additional, Becker, Jordan E., additional, Bornstein, Bavat, additional, Cosmanescu, Filip, additional, Schuldiner, Oren, additional, Mann, Richard S., additional, Honig, Barry, additional, and Shapiro, Lawrence, additional

Published
2024
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18. Structure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5

Author

Mangou, Khadidiatou, Moore, Adam J., Thiam, Laty Gaye, Ba, Aboubacar, Orfanó, Alessandra, Desamours, Ife, Ndegwa, Duncan Ndungu, Goodwin, Justin, Guo, Yicheng, Sheng, Zizhang, Patel, Saurabh D., Diallo, Fatoumata, Sene, Seynabou D., Pouye, Mariama N., Faye, Awa Thioub, Thiam, Alassane, Nunez, Vanessa, Diagne, Cheikh Tidiane, Sadio, Bacary Djilocalisse, Shapiro, Lawrence, Faye, Ousmane, Mbengue, Alassane, and Bei, Amy K.

Published
2022
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19. Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs

Author

Bepler, Tristan, Morin, Andrew, Brasch, Julia, Shapiro, Lawrence, Noble, Alex J., and Berger, Bonnie

Subjects
Quantitative Biology - Quantitative Methods, Computer Science - Computer Vision and Pattern Recognition, Statistics - Machine Learning
Abstract

Cryo-electron microscopy (cryoEM) is an increasingly popular method for protein structure determination. However, identifying a sufficient number of particles for analysis (often >100,000) can take months of manual effort. Current computational approaches are limited by high false positive rates and require significant ad-hoc post-processing, especially for unusually shaped particles. To address this shortcoming, we develop Topaz, an efficient and accurate particle picking pipeline using neural networks trained with few labeled particles by newly leveraging the remaining unlabeled particles through the framework of positive-unlabeled (PU) learning. Remarkably, despite using minimal labeled particles, Topaz allows us to improve reconstruction resolution by up to 0.15 {\AA} over published particles on three public cryoEM datasets without any post-processing. Furthermore, we show that our novel generalized-expectation criteria approach to PU learning outperforms existing general PU learning approaches when applied to particle detection, especially for challenging datasets of non-globular proteins. We expect Topaz to be an essential component of cryoEM analysis., Comment: 43 pages, 5 main figures, 6 supplemental figures

Published
2018
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20. Mutational fitness landscapes reveal genetic and structural improvement pathways for a vaccine-elicited HIV-1 broadly neutralizing antibody

Author

Madan, Bharat, Zhang, Baoshan, Xu, Kai, Chao, Cara W., O’Dell, Sijy, Wolfe, Jacy R., Chuang, Gwo-Yu, Fahad, Ahmed S., Geng, Hui, Kong, Rui, Louder, Mark K., Nguyen, Thuy Duong, Rawi, Reda, Schön, Arne, Sheng, Zizhang, Nimrania, Rajani, Wang, Yiran, Zhou, Tongqing, Lin, Bob C., Doria-Rose, Nicole A., Shapiro, Lawrence, Kwong, Peter D., and DeKosky, Brandon J.

Published
2021

21. Interactions between the Ig-Superfamily Proteins DIP-α and Dpr6/10 Regulate Assembly of Neural Circuits

Author

Xu, Shuwa, Xiao, Qi, Cosmanescu, Filip, Sergeeva, Alina P, Yoo, Juyoun, Lin, Ying, Katsamba, Phinikoula S, Ahlsen, Goran, Kaufman, Jonathan, Linaval, Nikhil T, Lee, Pei-Tseng, Bellen, Hugo J, Shapiro, Lawrence, Honig, Barry, Tan, Liming, and Zipursky, S Lawrence

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Generic health relevance, Animals, Animals, Genetically Modified, Clustered Regularly Interspaced Short Palindromic Repeats, Drosophila, Drosophila Proteins, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, HEK293 Cells, Humans, Medulla Oblongata, Mutation, Neuropil, Protein Interaction Maps, Surface Plasmon Resonance, Transcription Factors, Transfection, Visual Pathways, DIP/Dpr proteins, cell survival, connectome, development, layer-specific circuit, specificity, synapse, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Drosophila Dpr (21 paralogs) and DIP proteins (11 paralogs) are cell recognition molecules of the immunoglobulin superfamily (IgSF) that form a complex protein interaction network. DIP and Dpr proteins are expressed in a synaptic layer-specific fashion in the visual system. How interactions between these proteins regulate layer-specific synaptic circuitry is not known. Here we establish that DIP-α and its interacting partners Dpr6 and Dpr10 regulate multiple processes, including arborization within layers, synapse number, layer specificity, and cell survival. We demonstrate that heterophilic binding between Dpr6/10 and DIP-α and homophilic binding between DIP-α proteins promote interactions between processes in vivo. Knockin mutants disrupting the DIP/Dpr binding interface reveal a role for these proteins during normal development, while ectopic expression studies support an instructive role for interactions between DIPs and Dprs in circuit development. These studies support an important role for the DIP/Dpr protein interaction network in regulating cell-type-specific connectivity patterns.

Published
2018

22. Neuron-Subtype-Specific Expression, Interaction Affinities, and Specificity Determinants of DIP/Dpr Cell Recognition Proteins

Author

Cosmanescu, Filip, Katsamba, Phinikoula S, Sergeeva, Alina P, Ahlsen, Goran, Patel, Saurabh D, Brewer, Joshua J, Tan, Liming, Xu, Shuwa, Xiao, Qi, Nagarkar-Jaiswal, Sonal, Nern, Aljoscha, Bellen, Hugo J, Zipursky, S Lawrence, Honig, Barry, and Shapiro, Lawrence

Subjects
Biomedical and Clinical Sciences, Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Animals, Animals, Genetically Modified, Cell Communication, Drosophila Proteins, Drosophila melanogaster, HEK293 Cells, Humans, Medulla Oblongata, Membrane Proteins, Models, Molecular, Neurons, Protein Binding, Surface Plasmon Resonance, Transfection, Visual Pathways, Psychology, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Binding between DIP and Dpr neuronal recognition proteins has been proposed to regulate synaptic connections between lamina and medulla neurons in the Drosophila visual system. Each lamina neuron was previously shown to express many Dprs. Here, we demonstrate, by contrast, that their synaptic partners typically express one or two DIPs, with binding specificities matched to the lamina neuron-expressed Dprs. A deeper understanding of the molecular logic of DIP/Dpr interaction requires quantitative studies on the properties of these proteins. We thus generated a quantitative affinity-based DIP/Dpr interactome for all DIP/Dpr protein family members. This revealed a broad range of affinities and identified homophilic binding for some DIPs and some Dprs. These data, along with full-length ectodomain DIP/Dpr and DIP/DIP crystal structures, led to the identification of molecular determinants of DIP/Dpr specificity. This structural knowledge, along with a comprehensive set of quantitative binding affinities, provides new tools for functional studies in vivo.

Published
2018

24. Anti-idiotype isolation of a broad and potent influenza A virus-neutralizing human antibody.

Author

Olia, Adam S., Prabhakaran, Madhu, Harris, Darcy R., Cheung, Crystal Sao-Fong, Gillespie, Rebecca A., Gorman, Jason, Hoover, Abigayle, Morano, Nicholas C., Ourahmane, Amine, Srikanth, Abhinaya, Shuishu Wang, Weiwei Wu, Tongqing Zhou, Andrews, Sarah F., Masaru Kanekiyo, Shapiro, Lawrence, McDermott, Adrian B., and Kwong, Peter D.

Subjects
INFLUENZA, MOLECULAR mimicry, IMMUNOGLOBULINS, INFLUENZA A virus, INFLUENZA viruses
Abstract

The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate antiidiotype antibodies against germline versions of VH6-1 antibodies, use these to sort human leukocytes, and isolate a new VH6-1-class member, antibody L5A7, which potently neutralized diverse group 1 and group 2 influenza A strains. While its heavy chain derived from the canonical IGHV6-1 heavy chain gene used by the class, L5A7 utilized a light chain gene, IGKV1-9, which had not been previously observed in other VH6-1-class antibodies. The cryo-EM structure of L5A7 in complex with Indonesia 2005 hemagglutinin revealed a nearly identical binding mode to other VH6-1-class members. The structure of L5A7 bound to the isolating anti-idiotype antibody, 28H6E11, revealed a shared surface for binding anti-idiotype and hemagglutinin that included two critical L5A7 regions: an FG motif in the third heavy chain-complementary determining region (CDR H3) and the CDR L1 loop. Surprisingly, the chemistries of L5A7 interactions with hemagglutinin and with anti-idiotype were substantially different. Overall, we demonstrate anti-idiotype-based isolation of a broad and potent influenza A virus-neutralizing antibody, revealing that anti-idiotypic selection of antibodies can involve features other than chemical mimicry of the target antigen. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Astrocyte morphogenesis requires self-recognition

Author

Zipursky, S., primary, Lee, John, additional, Sergeeva, Alina, additional, Ahlsen, Goran, additional, Mannepalli, Seetha, additional, Bahna, Fabiana, additional, Goodman, Kerry, additional, Khakh, Baljit, additional, Weiner, Joshua, additional, Shapiro, Lawrence, additional, and Honig, Barry, additional

Published
2024
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27. Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies

Author

Cottrell, Christopher A., Manne, Kartik, Kong, Rui, Wang, Shuishu, Zhou, Tongqing, Chuang, Gwo-Yu, Edwards, Robert J., Henderson, Rory, Janowska, Katarzyna, Kopp, Megan, Lin, Bob C., Louder, Mark K., Olia, Adam S., Rawi, Reda, Shen, Chen-Hsiang, Taft, Justin D., Torres, Jonathan L., Wu, Nelson R., Zhang, Baoshan, Doria-Rose, Nicole A., Cohen, Myron S., Haynes, Barton F., Shapiro, Lawrence, Ward, Andrew B., Acharya, Priyamvada, Mascola, John R., and Kwong, Peter D.

Published
2021
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30. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7

Author

Wang, Pengfei, Nair, Manoj S., Liu, Lihong, Iketani, Sho, Luo, Yang, Guo, Yicheng, Wang, Maple, Yu, Jian, Zhang, Baoshan, Kwong, Peter D., Graham, Barney S., Mascola, John R., Chang, Jennifer Y., Yin, Michael T., Sobieszczyk, Magdalena, Kyratsous, Christos A., Shapiro, Lawrence, Sheng, Zizhang, Huang, Yaoxing, and Ho, David D.

Published
2021
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31. Embodied Cognition and Its Significance for Education

Author

Shapiro, Lawrence and Stolz, Steven A.

Abstract

Psychology has made, and continues to make, a significant contribution to the discipline area of education. Since one of the main aims of education concerns student learning -- which is an indisputably psychological phenomenon -- we argue that the emerging research agenda of embodied cognition has much to offer educational practitioners, researchers, and/or policy-makers. Although embodied cognition is still in its infancy, the multidisciplinary and interdisciplinary nature of the literature provides some thought-provoking recommendations to enhance educational practice or practices, which in turn can bring about student learning more effectively. Consequently, this article will be concerned with the discussion of two issues: first, we provide a brief historical overview that foregrounds embodied cognition, and, second, we outline the educational implications of embodied cognition through the use of some examples significant to education. We conclude with an argument for the importance of making findings in an area we call 'embodied education' available to teachers.

Published
2019
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35. Allosteric Neutralization by Human H7N9 Antibodies

Author

Wu, Xueling, primary, Jia, Manxue, additional, Zhao, HanJun, additional, Morano, Nicholas, additional, Lu, Hong, additional, Lui, Yin-Ming, additional, Du, Haijuan, additional, Becker, Jordan, additional, Yuen, Kwok-Yung, additional, Ho, David, additional, Kwong, Peter, additional, Shapiro, Lawrence, additional, and To, Kelvin Kai-Wang, additional

Published
2023
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36. Structure-based design of a single-chain triple-disulfide-stabilized fusion-glycoprotein trimer that elicits high-titer neutralizing responses against human metapneumovirus

Author

Ou, Li, primary, Chen, Steven J., additional, Teng, I-Ting, additional, Yang, Lijuan, additional, Zhang, Baoshan, additional, Zhou, Tongqing, additional, Biju, Andrea, additional, Cheng, Cheng, additional, Kong, Wing-Pui, additional, Morano, Nicholas C., additional, Stancofski, Erik-Stephane D., additional, Todd, John-Paul, additional, Tsybovsky, Yaroslav, additional, Wang, Shuishu, additional, Zheng, Cheng-Yan, additional, Mascola, John R., additional, Shapiro, Lawrence, additional, Woodward, Ruth A., additional, Buchholz, Ursula J., additional, and Kwong, Peter D., additional

Published
2023
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38. E-cadherin junction formation involves an active kinetic nucleation process

Author

Biswas, Kabir H, Hartman, Kevin L, Yu, Cheng-han, Harrison, Oliver J, Song, Hang, Smith, Adam W, Huang, William YC, Lin, Wan-Chen, Guo, Zhenhuan, Padmanabhan, Anup, Troyanovsky, Sergey M, Dustin, Michael L, Shapiro, Lawrence, Honig, Barry, Zaidel-Bar, Ronen, and Groves, Jay T

Subjects
Biochemistry and Cell Biology, Biological Sciences, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Biophysics, Cadherins, Cell Line, Cytoskeleton, Humans, Intercellular Junctions, Kinetics, Lipid Bilayers, Signal Transduction, cadherin, diffusion, adhesion, nucleation, bilayer
Abstract

Epithelial (E)-cadherin-mediated cell-cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in living cells and the extracellular domain of E-cadherin (E-cad-ECD) in a supported membrane. Junction formation in this hybrid live cell-supported membrane configuration requires both active processes within the living cell and a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit α-catenin and exhibit remodeled cortical actin. Observations suggest that the initial stages of junction formation in this hybrid system depend on the trans but not the cis interactions between E-cadherin molecules, and proceed via a nucleation process in which protrusion and retraction of filopodia play a key role.

Published
2015

39. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

Author

Liu, Lihong, Wang, Pengfei, Nair, Manoj S., Yu, Jian, Rapp, Micah, Wang, Qian, Luo, Yang, Chan, Jasper F.-W., Sahi, Vincent, Figueroa, Amir, Guo, Xinzheng V., Cerutti, Gabriele, Bimela, Jude, Gorman, Jason, Zhou, Tongqing, Chen, Zhiwei, Yuen, Kwok-Yung, Kwong, Peter D., Sodroski, Joseph G., Yin, Michael T., Sheng, Zizhang, Huang, Yaoxing, Shapiro, Lawrence, and Ho, David D.

Published
2020
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43. Structural and energetic determinants of adhesive binding specificity in type I cadherins

Author

Vendome, Jeremie, Felsovalyi, Klara, Song, Hang, Yang, Zhongyu, Jin, Xiangshu, Brasch, Julia, Harrison, Oliver J, Ahlsen, Goran, Bahna, Fabiana, Kaczynska, Anna, Katsamba, Phinikoula S, Edmond, Darwin, Hubbell, Wayne L, Shapiro, Lawrence, and Honig, Barry

Subjects
Emerging Infectious Diseases, Biotechnology, 1.1 Normal biological development and functioning, Underpinning research, Amino Acid Sequence, Animals, Binding, Competitive, Cadherins, Crystallography, X-Ray, Electron Spin Resonance Spectroscopy, HEK293 Cells, Humans, Hydrophobic and Hydrophilic Interactions, Kinetics, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Protein Binding, Protein Multimerization, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Static Electricity, Xenopus, Xenopus Proteins, cadherin dimerization, protein family design, entropy contribution
Abstract

Type I cadherin cell-adhesion proteins are similar in sequence and structure and yet are different enough to mediate highly specific cell-cell recognition phenomena. It has previously been shown that small differences in the homophilic and heterophilic binding affinities of different type I family members can account for the differential cell-sorting behavior. Here we use a combination of X-ray crystallography, analytical ultracentrifugation, surface plasmon resonance and double electron-electron resonance (DEER) electron paramagnetic resonance spectroscopy to identify the molecular determinants of type I cadherin dimerization affinities. Small changes in sequence are found to produce subtle structural and dynamical changes that impact relative affinities, in part via electrostatic and hydrophobic interactions, and in part through entropic effects because of increased conformational heterogeneity in the bound states as revealed by DEER distance mapping in the dimers. These findings highlight the remarkable ability of evolution to exploit a wide range of molecular properties to produce closely related members of the same protein family that have affinity differences finely tuned to mediate their biological roles.

Published
2014

47. 'Will They Fly a Plane into Our House?' How To Talk to Children about Terrorism.

Author

Shapiro, Lawrence E. and Shapiro, Lawrence E.

Abstract

This book is intended to help parents, teachers, and counselors of school-age children who did not experience the loss of someone close to them in the terrorist attacks of September 11, 2001, but who are still at risk for prolonged anxiety reactions. Although every child will react in a different way to these events, concerned adults must help each one communicate and cope. The first part of the book provides answers to parents' questions, with an emphasis on techniques for decreasing a child's stress and anxiety. The second part of the book provides answers to some of the most common questions that children ask about terrorism. The final part of the book provides emotional intelligence activities for enhancing 10 emotional skills that children need to develop in order to cope better with a national trauma like the terrorist attacks, or with a personal problem that is causing anxiety and worry. (GCP)

Published
2001

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