De novo design of obligate ABC-type heterotrimeric proteins.
De novo design of obligate ABC-type heterotrimeric proteins.
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DOI：
10.1038/s41594-022-00879-4
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发表时间：
2022-12
影响因子：
16.8
通讯作者：
Baker, David
中科院分区：
文献类型：
--
作者：
Bermeo, Sherry;Favor, Andrew;Chang, Ya-Ting;Norris, Andrew;Boyken, Scott E.;Hsia, Yang;Haddox, Hugh K.;Xu, Chunfu;Brunette, T. J.;Wysocki, Vicki H.;Bhabha, Gira;Ekiert, Damian C.;Baker, David
The de novo design of three protein chains that associate to form a heterotrimer (but not any of the possible two-chain heterodimers) and that can drive the assembly of higher-order branching structures is an important challenge for protein design. We designed helical heterotrimers with specificity conferred by buried hydrogen bond networks and large aromatic residues to enhance shape complementary packing. We obtained ten designs for which all three chains cooperatively assembled into heterotrimers with few or no other species present. Crystal structures of a helical bundle heterotrimer and extended versions, with helical repeat proteins fused to individual subunits, showed all three chains assembling in the designed orientation. We used these heterotrimers as building blocks to construct larger cyclic oligomers, which were structurally validated by electron microscopy. Our three-way junction designs provide new routes to complex protein nanostructures and enable the scaffolding of three distinct ligands for modulation of cell signaling. ABC-type heterotrimeric proteins can be designed de novo using coiled coils and helical bundles as starting scaffolds, extended using helical repeat proteins and then used as building blocks for higher-order oligomeric assemblies.
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影响因子：
5.6
作者：
Grigoryan G;Degrado WF
通讯作者：
Degrado WF
影响因子：
16.6
作者：
Hiranuma N;Park H;Baek M;Anishchenko I;Dauparas J;Baker D
通讯作者：
Baker D
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1007/978-1-62703-691-7_18
发表时间：
2014
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Dyer, Kevin N;Hammel, Michal;Rambo, Robert P;Tsutakawa, Susan E;Rodic, Ivan;Classen, Scott;Tainer, John A;Hura, Greg L
通讯作者：
Hura, Greg L
影响因子：
15
作者：
Fallas, Jorge A.;Lee, Michael A.;Hartgerink, Jeffrey D.
通讯作者：
Hartgerink, Jeffrey D.