Marcos Pires

Abstract

Abstract

An attractive, but as yet generally unrealized, approach to cancer therapy concerns discovering agents that change the state of differentiation of the cancer cells. Recently, we discovered a phenomenon that we call “receptor pleiotropism” in which agonist antibodies against known receptors induce cell fates that are very different from those...

Nature advance online publication 21 October 2015. doi:10.1038/nature15709

Authors: Arthur Prindle, Jintao Liu, Munehiro Asally, San Ly, Jordi Garcia-Ojalvo & Gürol M. Süel

Nature advance online publication 21 October 2015. doi:10.1038/nature15644

Authors: Isaac S. Harris & Joan S. Brugge

Reactive oxygen species have been viewed as stress-inducing molecules that promote cancer initiation. But new evidence indicates that oxidative stress can be beneficial — inhibiting the spread of a cancer to other sites.

Nature Reviews Immunology 15, 375 (2015). doi:10.1038/nri3837

Authors: Maria Kaparakis-Liaskos & Richard L. Ferrero

Gram-negative bacteria shed extracellular outer membrane vesicles (OMVs) during their normal growth both in vitro and in vivo. OMVs are spherical, bilayered membrane nanostructures that contain many components found within the parent bacterium. Until recently, OMVs were dismissed as a by-product of bacterial

Nature Medicine. doi:10.1038/nm.3954

Authors: Hui Gao, Joshua M Korn, Stéphane Ferretti, John E Monahan, Youzhen Wang, Mallika Singh, Chao Zhang, Christian Schnell, Guizhi Yang, Yun Zhang, O Alejandro Balbin, Stéphanie Barbe, Hongbo Cai, Fergal Casey, Susmita Chatterjee, Derek Y Chiang, Shannon Chuai, Shawn M Cogan, Scott D Collins, Ernesta Dammassa, Nicolas Ebel, Millicent Embry, John Green, Audrey Kauffmann, Colleen Kowal, Rebecca J Leary, Joseph Lehar, Ying Liang, Alice Loo, Edward Lorenzana, E Robert McDonald, Margaret E McLaughlin, Jason Merkin, Ronald Meyer, Tara L Naylor, Montesa Patawaran, Anupama Reddy, Claudia Röelli, David A Ruddy, Fernando Salangsang, Francesca Santacroce, Angad P Singh, Yan Tang, Walter Tinetto, Sonja Tobler, Roberto Velazquez, Kavitha Venkatesan, Fabian Von Arx, Hui Qin Wang, Zongyao Wang, Marion Wiesmann, Daniel Wyss, Fiona Xu, Hans Bitter, Peter Atadja, Emma Lees, Francesco Hofmann, En Li, Nicholas Keen, Robert Cozens, Michael Rugaard Jensen, Nancy K Pryer, Juliet A Williams & William R Sellers

Article

Advances in bionanotechnology demand an increased portfolio of assemblies beyond those currently available. Here, the authors design a crystallographically characterized super-helical sequence composed of single heptad repeats which, through derivatisation, offers vast potential applications.

Nature Communications doi: 10.1038/ncomms9615

Authors: Sudipta Mondal, Lihi Adler-Abramovich, Ayala Lampel, Yaron Bram, Sophia Lipstman, Ehud Gazit

Interacting proteins can coevolve through the generation of promiscuous variants, which serve as mutational intermediates that preserve the ability of the two proteins to functionally interact while they evolve.

There is growing interest in using engineered cells as therapeutic agents. For example, synthetic chimeric antigen receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, these engineered T cells can exhibit excessive activity that is difficult to control and can cause severe toxicity. We designed “ON-switch” CARs that enable small-molecule control over T cell therapeutic functions while still retaining antigen specificity. In these split receptors, antigen-binding and intracellular signaling components assemble only in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate cell-autonomous recognition and user control. Authors: Chia-Yung Wu, Kole T. Roybal, Elias M. Puchner, James Onuffer, Wendell A. Lim

Nature advance online publication 14 October 2015. doi:10.1038/nature15726

Authors: Elena Piskounova, Michalis Agathocleous, Malea M. Murphy, Zeping Hu, Sara E. Huddlestun, Zhiyu Zhao, A. Marilyn Leitch, Timothy M. Johnson, Ralph J. DeBerardinis & Sean J. Morrison

Peptidoglycan (PG), a complex polymer composed of saccharide chains cross-linked by short peptides, is a critical component of the bacterial cell wall. PG synthesis has been extensively studied in model organisms but remains poorly understood in mycobacteria, a genus that includes the important human pathogen Mycobacterium tuberculosis (Mtb). The principle...

α-Helical antimicrobial peptides (AMPs) generally have facially amphiphilic structures that may lead to undesired peptide interactions with blood proteins and self-aggregation due to exposed hydrophobic surfaces. Here we report the design of a class of cationic, helical homo-polypeptide antimicrobials with a hydrophobic internal helical core and a charged exterior shell,...

Article

Cell shape is determined by a combination of biochemical regulation and mechanical forces. By imaging the dynamic behaviour of growth regulatory proteins in fission yeast and integrating these data within a mechanical model, Abenza et al . find that exocytosis plays a dominant role in shaping growth domains.

Nature Communications doi: 10.1038/ncomms9400

Authors: Juan F. Abenza, Etienne Couturier, James Dodgson, Johanna Dickmann, Anatole Chessel, Jacques Dumais, Rafael E. Carazo Salas

Article

Typically, in order to form large peptides, complex procedures or activating agents are required. Here, the authors show that simple aqueous conditions with dehydration-hydration cycles are sufficient for the oligomerization of amino acids into peptides (up to 20 amino acids long) in yields of up to 50%.

Nature Communications doi: 10.1038/ncomms9385

Authors: Marc Rodriguez-Garcia, Andrew J. Surman, Geoffrey J.T. Cooper, Irene Suárez-Marina, Zied Hosni, Michael P. Lee, Leroy Cronin

Cellulose biosynthesis in plant secondary cell walls forms the basis of vascular development in land plants, with xylem tissues constituting the vast majority of terrestrial biomass. We used plant lines that contained an inducible master transcription factor controlling xylem cell fate to quantitatively image fluorescently tagged cellulose synthase enzymes during cellulose deposition in living protoxylem cells. The formation of secondary cell wall thickenings was associated with a redistribution and enrichment of CESA7-containing cellulose synthase complexes (CSCs) into narrow membrane domains. The velocities of secondary cell wall–specific CSCs were faster than those of primary cell wall CSCs during abundant cellulose production. Dynamic intracellular of endomembranes, in combination with increased velocity and high density of CSCs, enables cellulose to be synthesized rapidly in secondary cell walls. Authors: Y. Watanabe, M. J. Meents, L. M. McDonnell, S. Barkwill, A. Sampathkumar, H. N. Cartwright, T. Demura, D. W. Ehrhardt, A.L. Samuels, S. D. Mansfield

Nature advance online publication 07 October 2015. doi:10.1038/nature15363

Authors: Ranjan V. Mannige, Thomas K. Haxton, Caroline Proulx, Ellen J. Robertson, Alessia Battigelli, Glenn L. Butterfoss, Ronald N. Zuckermann & Stephen Whitelam

A promising route to the synthesis of protein-mimetic materials that are capable of complex functions, such as molecular recognition and catalysis, is provided by sequence-defined peptoid polymers—structural relatives of biologically occurring polypeptides. Peptoids, which are relatively non-toxic and resistant to degradation, can fold into defined structures through a combination of sequence-dependent interactions. However, the range of possible structures that are accessible to peptoids and other biological mimetics is unknown, and our ability to design protein-like architectures from these polymer classes is limited. Here we use molecular-dynamics simulations, together with scattering and microscopy data, to determine the atomic-resolution structure of the recently discovered peptoid nanosheet, an ordered supramolecular assembly that extends macroscopically in only two dimensions. Our simulations show that nanosheets are structurally and dynamically heterogeneous, can be formed only from peptoids of certain lengths, and are potentially porous to water and ions. Moreover, their formation is enabled by the peptoids’ adoption of a secondary structure that is not seen in the natural world. This structure, a zigzag pattern that we call a Σ(‘sigma’)-strand, results from the ability of adjacent backbone monomers to adopt opposed rotational states, thereby allowing the backbone to remain linear and untwisted. Linear backbones tiled in a brick-like way form an extended two-dimensional nanostructure, the Σ-sheet. The binary rotational-state motif of the Σ-strand is not seen in regular protein structures, which are usually built from one type of rotational state. We also show that the concept of building regular structures from multiple rotational states can be generalized beyond the peptoid nanosheet system.

Abstract

We recently described general principles for designing ideal protein structures stabilized by completely consistent local and nonlocal interactions. The principles relate secondary structure patterns to tertiary packing motifs and enable design of different protein topologies. To achieve fine control over protein shape and size within a particular topology, we have...

Paramyxoviruses include many important animal and human pathogens. Most paramyxoviruses have two integral membrane proteins: fusion protein (F) and attachment proteins hemagglutinin, hemagglutinin–neuraminidase, or glycoprotein (G), which are critical for viral entry into cells. J paramyxovirus (JPV) encodes four integral membrane proteins: F, G, SH, and transmembrane (TM). The function...