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Improving Protein Expression, Stability, and Function with ProteinMPNN.
Sumida, Kiera H; Núñez-Franco, Reyes; Kalvet, Indrek; Pellock, Samuel J; Wicky, Basile I M; Milles, Lukas F; Dauparas, Justas; Wang, Jue; Kipnis, Yakov; Jameson, Noel; Kang, Alex; De La Cruz, Joshmyn; Sankaran, Banumathi; Bera, Asim K; Jiménez-Osés, Gonzalo; Baker, David.
Afiliación
  • Sumida KH; Department of Chemistry, University of Washington, Seattle, Washington 98195, United States.
  • Núñez-Franco R; Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
  • Kalvet I; Center for Cooperative Research in Biosciences, Basque Research and Technology Alliance, Derio 48160, Spain.
  • Pellock SJ; Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
  • Wicky BIM; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States.
  • Milles LF; Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, United States.
  • Dauparas J; Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
  • Wang J; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States.
  • Kipnis Y; Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
  • Jameson N; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States.
  • Kang A; Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
  • De La Cruz J; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States.
  • Sankaran B; Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
  • Bera AK; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States.
  • Jiménez-Osés G; Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
  • Baker D; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States.
J Am Chem Soc ; 146(3): 2054-2061, 2024 01 24.
Article en En | MEDLINE | ID: mdl-38194293
ABSTRACT
Natural proteins are highly optimized for function but are often difficult to produce at a scale suitable for biotechnological applications due to poor expression in heterologous systems, limited solubility, and sensitivity to temperature. Thus, a general method that improves the physical properties of native proteins while maintaining function could have wide utility for protein-based technologies. Here, we show that the deep neural network ProteinMPNN, together with evolutionary and structural information, provides a route to increasing protein expression, stability, and function. For both myoglobin and tobacco etch virus (TEV) protease, we generated designs with improved expression, elevated melting temperatures, and improved function. For TEV protease, we identified multiple designs with improved catalytic activity as compared to the parent sequence and previously reported TEV variants. Our approach should be broadly useful for improving the expression, stability, and function of biotechnologically important proteins.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endopeptidasas Idioma: En Revista: J Am Chem Soc Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endopeptidasas Idioma: En Revista: J Am Chem Soc Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos