9CCF

Crystal Structure of DA7-2

Summary for 9CCF

• Entry DOI: 10.2210/pdb9ccf/pdb
• Descriptor: DA7_2 (1 entity in total)
• Functional Keywords: de novo design, disorder, intrinsically disordered protein, de novo protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 56357.91

Authors

Bera, A.K.,Wu, K.,Kang, A.,Baker, D. (deposition date: 2024-06-21, release date: 2025-08-13)

Primary citation

Wu, K.,Jiang, H.,Hicks, D.R.,Liu, C.,Muratspahic, E.,Ramelot, T.A.,Liu, Y.,McNally, K.,Kenny, S.,Mihut, A.,Gaur, A.,Coventry, B.,Chen, W.,Bera, A.K.,Kang, A.,Gerben, S.,Lamb, M.Y.,Murray, A.,Li, X.,Kennedy, M.A.,Yang, W.,Song, Z.,Schober, G.,Brierley, S.M.,O'Neill, J.,Gelb, M.H.,Montelione, G.T.,Derivery, E.,Baker, D.
Design of intrinsically disordered region binding proteins.
Science, 389:eadr8063-eadr8063, 2025

PubMed Abstract: Intrinsically disordered proteins and peptides play key roles in biology, but a lack of defined structures and high variability in sequence and conformational preferences have made targeting such systems challenging. We describe a general approach for designing proteins that bind intrinsically disordered protein regions in diverse extended conformations with side chains fitting into complementary binding pockets. We used the approach to design binders for 39 highly diverse unstructured targets, including polar targets, and obtained designs with 100-picomolar to 100-nanomolar affinities in 34 cases, testing ~22 designs per target. The designs function in cells and as detection reagents and are specific for their intended targets in all-by-all binding experiments. Our approach is a major step toward a general solution to the intrinsically disordered protein and peptide recognition problem.

PubMed: 40674483
DOI: 10.1126/science.adr8063

Experimental method

X-RAY DIFFRACTION (4 Å)