Macromolecular crowding impact on anti-CRISPR AcrIIC3/NmeCas9 complex: Insights from scaled particle theory, molecular dynamics, and elastic networks models.

Autor: Delgado A; Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Laboratorio de Química Biofísica Teórica y Experimental (LQBTE), 4001 Maracaibo, Zulia, Venezuela; Universidad del Zulia (LUZ), Facultad Experimental de Ciencias (FEC), Departamento de Química, Laboratorio de Química Teórica y Computacional (LQTC), 4001 Maracaibo, Venezuela., Vera-Villalobos J; Facultad de Ciencias Naturales y Matemáticas, Departamento de Química y Ciencias Ambientales, Laboratorio de Análisis Químico Instrumental (LAQUINS), Escuela Superior Politécnica del Litoral, Guayaquil, Ecuador., Paz JL; Departamento Académico de Química Inorgánica, Facultad de Química e Ingeniería Química, Universidad Nacional Mayor de San Marcos, Lima, Peru., Lossada C; Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Laboratorio de Biocomputación (LB), 4001 Maracaibo, Zulia, Venezuela., Hurtado-León ML; Universidad del Zulia (LUZ), Facultad Experimental de Ciencias (FEC), Departamento de Biología, Laboratorio de Genética y Biología Molecular (LGBM), 4001 Maracaibo, Venezuela., Marrero-Ponce Y; Universidad San Francisco de Quito (USFQ), Grupo de Medicina Molecular y Traslacional (MeM&T), Colegio de Ciencias de la Salud (COCSA), Escuela de Medicina, Edificio de Especialidades Médicas, Quito 170157, Pichincha, Ecuador; Departamento de Ciencias de la Computación, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California 22860, Mexico; Instituto de Simulación Computacional (ISC-USFQ), Diego de Robles y vía Interoceánica, Quito 170157, Pichincha, Ecuador., Toro-Mendoza J; Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Laboratorio de Química Biofísica Teórica y Experimental (LQBTE), 4001 Maracaibo, Zulia, Venezuela., Alvarado YJ; Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Laboratorio de Química Biofísica Teórica y Experimental (LQBTE), 4001 Maracaibo, Zulia, Venezuela. Electronic address: alvaradoysaias@gmail.com., González-Paz L; Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Laboratorio de Biocomputación (LB), 4001 Maracaibo, Zulia, Venezuela. Electronic address: lgonzalezpaz@gmail.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2023 Jul 31; Vol. 244, pp. 125113. Date of Electronic Publication: 2023 May 29.
DOI: 10.1016/j.ijbiomac.2023.125113
Abstrakt: The coupling of Cas9 and its inhibitor AcrIIC3, both from the bacterium Neisseria meningitidis (Nme), form a homodimer of the (NmeCas9/AcrIIC3) 2 type. This coupling was studied to assess the impact of their interaction with the crowders in the following environments: (1) homogeneous crowded, (2) heterogeneous, and (3) microheterogeneous cytoplasmic. For this, statistical thermodynamic models based on the scaled particle theory (SPT) were used, considering the attractive and repulsive protein-crowders contributions and the stability of the formation of spherocylindrical homodimers and the effects of changes in the size of spherical dimers were estimated. Studies based on models of dynamics, elastic networks, and statistical potentials to the formation of complexes NmeCas9/AcrIIC3 using PEG as the crowding agent support the predictions from SPT. Macromolecular crowding stabilizes the formation of the dimers, being more significant when the attractive protein-crowder interactions are weaker and the crowders are smaller. The coupling is favored towards the formation of spherical and compact dimers due to crowding addition (excluded-volume effects) and the thermodynamic stability of the dimers is markedly dependent on the size of the crowders. These results support the experimental mechanistic proposal of inhibition of NmeCas9 mediated by AcrIIC3.
Competing Interests: Declaration of competing interest The authors declare that there are no competing/financial interests.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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