Speaker1: Igor Polikarpov, Sao Carlos Institute of Physics, University of Sao Paulo, SP, Brazil
Title: Complex carbohydrate-active enzymes and their biomedical and biotechnological applications
Abstract: Enzymatic valorization of plant biomass is one of the most promising and sustainable routes for innovation in this area. Carbohydrates, such as mono- and oligosaccharides and polysaccharides, play extremely important roles in all forms of life, participating in host-pathogen interactions, signal transduction, inflammation, and fungal and bacterial biofilm formation. In addition, carbohydrates make up about three quarters of renewable plant biomass (~135 billion tons/year) with cell walls and reserve carbohydrates representing a sustainable resource of energy and renewable materials applications. However, our current understanding of synthesis and enzymatic degradation of plant complex carbohydrates is disproportionally incomplete. Therefore, systematic structural, biochemical and enzymatic studies of CAZymes with potential in depolymerization and synthesis of polysaccharides, aiming for better understanding of their molecular mechanisms of activities and specificities toward cognate substrates are crucial [1-5]. In our presentation, we discuss biotechnological applications of CAZymes and describe some of our structural and biochemical studies of these enzymes and their ‘green’ applications in Biotechnology and Biomedicine.
1. Alessi, A. et al. “Revealing the insoluble metasecretome of lignocellulose-degrading microbial communities” Scientific Reports (2017) 7: 2356. doi:10.1038/s41598-017-02506-5
2. Godoy, A.S. et al. “Structure, computational and biochemical analysis of PcCel45A endoglucanase from Phanerochaete chrysosporium and catalytic mechanisms of GH45 subfamily C members” Scientific Reports (2018) 8:3678. doi:10.1038/s41598-018-21798-9
3. Sepulchro, A. G. V., Vacilotto, M. M., Dias, L. D., Pellegrini, V. O., Velasco, J., Inada, N. M., Fernando Segato & Polikarpov, I. Light‐driven Lytic Polysaccharide Monooxygenase Catalysis Mediated by Type I Photosensitizers. ChemBioChem. (2024) 25(23), e202400486 (https://doi.org/10.1002/cbic.202400486)
4. Kadowaki, M.A.S., et al. “Unlocking the structural features for the xylobiohydrolase activity of an unusual GH11 member identified in a compost-derived consortium” Biotechnology and Bioengineering (2021) 118: 4052-4064. https://doi.org/10.1002/bit.27880
5. de Mello Capetti, C.C., et al. "Enzymatic production of xylooligosaccharides from corn cobs: Assessment of two different pretreatment strategies." Carbohydrate Polymers (2023) 299: 120174. https://doi.org/10.1016/j.carbpol.2022.120174
This work was supported by Conselho Nac. Des. Cient. Tecnologico (CNPq # 306852/2021-7 & 440180/2022-8) and by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, #2021/08780-1 & 2024/00533-3.
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Speaker2: Paulo Cesar Telles de Souza, Centre Blaise Pascal de Simulation et de Modélisation Numérique, Ecole Normale Supérieure de Lyon
Title: Dynamic Protein Interfaces in Membrane Environments Revealed by Coarse-Grained Simulations
Abstract: Protein–protein interfaces in membranes are intrinsically dynamic and tightly coupled to their lipid environment. Their stability, organization, and functional transitions are modulated by membrane composition, curvature, and thickness, making them fundamentally distinct from soluble protein complexes. Membrane protein assemblies can reshape their local surroundings by inducing curvature, altering bilayer thickness, or promoting the enrichment or depletion of specific lipid species [1]. These perturbations are not static: they evolve as proteins undergo conformational changes, oligomerization, or activity-dependent rearrangements. Despite remarkable progress in structural and biophysical techniques, capturing this dynamic interplay across relevant spatial and temporal scales remains challenging. To access these coupled protein–lipid processes, we employ coarse-grained molecular dynamics simulations using the Martini models [2]. The current generation, Martini 3 [3], enables the exploration of large membrane assemblies while retaining a chemically meaningful description of intermolecular interactions. This framework allows us to probe interface plasticity, lipid-mediated stabilization mechanisms, and membrane remodeling effects over extended timescales.
In this talk, I will discuss how coarse-grained simulations reveal mechanistic principles governing membrane protein interfaces across different levels of complexity. Examples range from transmembrane peptide dimers [4], where alternate configurations are sampled in a lipid-dependent manner, to large multicomponent systems such as energy-coupling factor (ECF) transporters [5] and the human signal peptidase complex (SPC) [6]. Across these systems, simulations uncover how membrane properties and protein conformational landscapes are reciprocally coupled, shaping interface stability and functional transitions. Together, these results illustrate how mesoscale modeling bridges structural snapshots and cellular function, providing a predictive framework to rationalize membrane protein organization in complex lipid environments.
1. Marrink SJ, Corradi V, Souza PCT, Ingólfsson HI, Tieleman DP, Sansom MSP. Computational Modeling of Realistic Cell Membranes. Chem Rev. 2019; 119:6184–226.
2.Marrink SJ, Monticelli L, Melo MN, Alessandri R, Tieleman DP, Souza PCT. Two decades of Martini: Better beads, broader scope. WIREs Comput Mol Sci. 2022.
3. Souza PCT, Alessandri R, Barnoud J, Thallmair S, Faustino I, Grünewald F, et al. Martini 3: a general-purpose force field for coarse-grained molecular dynamics. Nat Methods. 2021; 18:382–388.
4. Sahoo AR, Souza PCT, Meng Z, Buck M. Transmembrane dimers of type 1 receptors sample alternate configurations: MD simulations using coarse grain Martini 3 versus AlphaFold2 Multimer. Structure. 2023; 31:1-11.
5. Thangaratnarajah C, Souza PCT, et al. Expulsion mechanism of the substrate-translocating subunit in ECF transporters. Nature Communications. 2023. https://doi.org/10.1038/s41467-023-40266-1.
6. Liaci AM, Steigenberger B, Souza PCT, et al. Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage. Molecular Cell. 2021; 81(18):3934-3948.
Invited by Pierre-Damien Coureux
