9OIB
Mouse LRRC15 extracellular domain
Summary for 9OIB
| Entry DOI | 10.2210/pdb9oib/pdb |
| Descriptor | Leucine-rich repeat-containing protein 15, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | leucine-rich repeat repeat signal receptor, signaling protein |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 51993.99 |
| Authors | Wendorff, T.J.,Tombling, B. (deposition date: 2025-05-06, release date: 2026-05-13, Last modification date: 2026-07-22) |
| Primary citation | Tombling, B.J.,Cai, F.,Wendorff, T.J.,Ogasawara, A.,Gill, H.S.,Tinianow, J.N.,Chang, A.,Balana, A.T.,Peng, L.,Miller, S.E.,Walters, B.T.,Lictao, A.,Yu, Q.,DeWitt, D.C.,Wei, Y.,Wu, S.Z.,Sudhamsu, J.,Krishnamurty, A.T.,Williams, S.P.,Marik, J.,Zhang, Y.,Maun, H.R.,Kirchhofer, D. Development of LRRC15-binding disulfide-constrained peptides for PET imaging of cancer-associated fibroblasts. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Leucine-rich-repeat-containing protein 15 (LRRC15) is selectively expressed on cancer-associated fibroblasts (CAFs) and constitutes a promising biomarker for imaging the tumor microenvironment. Using a combinatorial library approach, assisted by machine learning, we developed disulfide-constrained peptides (DCPs), notably ML-YSD-07 and ML-PD-03, that demonstrate subnanomolar affinities for murine LRRC15 (muLRRC15) and specifically localize onto muLRRC15-expressing fibroblasts. PET imaging with F-radiolabeled ML-YSD-07 exhibits specific tumor accumulation in a murine pancreatic cancer model highly enriched with LRRC15-expressing CAFs. Crystal structures of apo-muLRRC15 and of ML-YSD-07-bound muLRRC15 show that the DCPs evolved to adopt a distinct binding conformation that efficiently interacts with a flat epitope on muLRRC15. Collectively, this work identifies potent, molecularly engineered LRRC15-binding peptides and further highlights LRRC15 as a valuable CAF biomarker for cancer imaging applications. PubMed: 42248838DOI: 10.1038/s41467-026-73845-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.26 Å) |
Structure validation
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