9H71
KIT123-KITbp complex (Domains D1-3 of the human receptor tyrosine kinase KIT complexed with the de novo designed minibinder KITbp)
Summary for 9H71
| Entry DOI | 10.2210/pdb9h71/pdb |
| Descriptor | Mast/stem cell growth factor receptor Kit, KITbp (de novo designed minibinder protein towards the receptor tyrosine kinase KIT), 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | de novo minibinder, rfdiffusion, receptor tyrosine kinase iii, cytokine receptor, protein binding |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 84142.28 |
| Authors | Toul, M.,Verschueren, K.H.G.,Verstraete, K.,Savvides, S.N. (deposition date: 2024-10-25, release date: 2026-01-21, Last modification date: 2026-02-11) |
| Primary citation | Sappington, I.,Toul, M.,Lee, D.S.,Robinson, S.A.,Goreshnik, I.,McCurdy, C.,Chan, T.C.,Buchholz, N.,Huang, B.,Vafeados, D.,Garcia-Sanchez, M.,Roullier, N.,Glogl, M.,Kim, C.J.,Watson, J.L.,Torres, S.V.,Verschueren, K.H.G.,Verstraete, K.,Hinck, C.S.,Benard-Valle, M.,Coventry, B.,Sims, J.N.,Ahn, G.,Wang, X.,Hinck, A.P.,Jenkins, T.P.,Ruohola-Baker, H.,Banik, S.M.,Savvides, S.N.,Baker, D. Improved protein binder design using beta-pairing targeted RFdiffusion. Nat Commun, 17:1101-1101, 2026 Cited by PubMed Abstract: Designing proteins that bind with high affinity to hydrophilic protein target sites remains a challenging problem. Here we show that RFdiffusion can be conditioned to generate protein scaffolds that form geometrically matched extended β-sheets with target protein edge β-strands in which polar groups on the target are complemented with hydrogen bonding groups on the design. We use this approach to design binders against edge-strand target sites on KIT, PDGFRɑ, ALK-2, ALK-3, FCRL5, NRP1, and α-CTX, and obtain higher (pM to mid nM) affinities and success rates than unconditioned RFdiffusion. Despite sharing β-strand interactions, designs have high specificity, reflecting the precise customization of interacting β-strand geometry and additional designed binder-target interactions. A binder-KIT co-crystal structure is nearly identical to the design model, confirming the accuracy of the design approach. The ability to robustly generate binders to the hydrophilic interaction surfaces of exposed β-strands considerably increases the range of computational binder design. PubMed: 41519838DOI: 10.1038/s41467-025-67866-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
Download full validation report
