Reconfigurable asymmetric protein assemblies through implicit negative design.

Autor: Sahtoe DD; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA., Praetorius F; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Courbet A; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA., Hsia Y; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Wicky BIM; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Edman NI; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195, USA.; Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA., Miller LM; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Timmermans BJR; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Decarreau J; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Morris HM; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Kang A; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Bera AK; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Baker D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Jan 21; Vol. 375 (6578), pp. eabj7662. Date of Electronic Publication: 2022 Jan 21.
DOI: 10.1126/science.abj7662
Abstrakt: Asymmetric multiprotein complexes that undergo subunit exchange play central roles in biology but present a challenge for design because the components must not only contain interfaces that enable reversible association but also be stable and well behaved in isolation. We use implicit negative design to generate β sheet-mediated heterodimers that can be assembled into a wide variety of complexes. The designs are stable, folded, and soluble in isolation and rapidly assemble upon mixing, and crystal structures are close to the computational models. We construct linearly arranged hetero-oligomers with up to six different components, branched hetero-oligomers, closed C4-symmetric two-component rings, and hetero-oligomers assembled on a cyclic homo-oligomeric central hub and demonstrate that such complexes can readily reconfigure through subunit exchange. Our approach provides a general route to designing asymmetric reconfigurable protein systems.
Databáze: MEDLINE
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