7JH5

Co-LOCKR: de novo designed protein switch

Summary for 7JH5

• Entry DOI: 10.2210/pdb7jh5/pdb
• Descriptor: Co-LOCKR: de novo designed protein switch (2 entities in total)
• Functional Keywords: helical bundle, protein switch, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 65759.66

Authors

Bick, M.J.,Lajoie, M.J.,Boyken, S.E.,Sankaran, B.,Baker, D. (deposition date: 2020-07-20, release date: 2020-09-02, Last modification date: 2024-04-03)

Primary citation

Lajoie, M.J.,Boyken, S.E.,Salter, A.I.,Bruffey, J.,Rajan, A.,Langan, R.A.,Olshefsky, A.,Muhunthan, V.,Bick, M.J.,Gewe, M.,Quijano-Rubio, A.,Johnson, J.,Lenz, G.,Nguyen, A.,Pun, S.,Correnti, C.E.,Riddell, S.R.,Baker, D.
Designed protein logic to target cells with precise combinations of surface antigens.
Science, 369:1637-1643, 2020

PubMed Abstract: Precise cell targeting is challenging because most mammalian cell types lack a single surface marker that distinguishes them from other cells. A solution would be to target cells using specific combinations of proteins present on their surfaces. In this study, we design colocalization-dependent protein switches (Co-LOCKR) that perform AND, OR, and NOT Boolean logic operations. These switches activate through a conformational change only when all conditions are met, generating rapid, transcription-independent responses at single-cell resolution within complex cell populations. We implement AND gates to redirect T cell specificity against tumor cells expressing two surface antigens while avoiding off-target recognition of single-antigen cells, and three-input switches that add NOT or OR logic to avoid or include cells expressing a third antigen. Thus, de novo designed proteins can perform computations on the surface of cells, integrating multiple distinct binding interactions into a single output.

PubMed: 32820060
DOI: 10.1126/science.aba6527

Experimental method

X-RAY DIFFRACTION (2.103 Å)