8U5A

Improving protein expression, stability, and function with ProteinMPNN

Summary for 8U5A

• Entry DOI: 10.2210/pdb8u5a/pdb
• Descriptor: Designed myoglobin, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• Functional Keywords: protein expression, stability, function, proteinmpnn, de novo design, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 40210.98

Authors

Kalvet, I.,Bera, A.K.,Baker, D. (deposition date: 2023-09-12, release date: 2024-01-17, Last modification date: 2024-01-31)

Primary citation

Sumida, K.H.,Nunez-Franco, R.,Kalvet, I.,Pellock, S.J.,Wicky, B.I.M.,Milles, L.F.,Dauparas, J.,Wang, J.,Kipnis, Y.,Jameson, N.,Kang, A.,De La Cruz, J.,Sankaran, B.,Bera, A.K.,Jimenez-Oses, G.,Baker, D.
Improving Protein Expression, Stability, and Function with ProteinMPNN.
J.Am.Chem.Soc., 146:2054-2061, 2024

PubMed 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.

PubMed: 38194293
DOI: 10.1021/jacs.3c10941

Experimental method

X-RAY DIFFRACTION (2 Å)