Summary for 9J7L
| Entry DOI | 10.2210/pdb9j7l/pdb |
| EMDB information | 61206 |
| Descriptor | Capsid protein, Carboxypeptidase D (2 entities in total) |
| Functional Keywords | receptor, aav8, complex, viral protein/hydrolase, viral protein-hydrolase complex |
| Biological source | Adeno-associated virus - 8 More |
| Total number of polymer chains | 7 |
| Total formula weight | 541983.78 |
| Authors | Xu, H.,Wang, G.P.,Su, X.D. (deposition date: 2024-08-19, release date: 2025-07-23, Last modification date: 2025-09-24) |
| Primary citation | Dhungel, B.P.,Xu, H.,Nagarajah, R.,Vitale, J.,Wong, A.C.H.,Gokal, D.,Feng, Y.,Tabar, M.S.,Metierre, C.,Parsania, C.,Song, X.,Wang, G.,Su, X.D.,Bailey, C.G.,Rasko, J.E.J. An alternate receptor for adeno-associated viruses. Cell, 188:4924-, 2025 Cited by PubMed Abstract: Systemic gene therapy using adeno-associated virus (AAV) vectors is approved for the treatment of several genetic disorders, but challenges and toxicities associated with high vector doses remain. We report an alternate receptor for AAV (AAVR2, carboxypeptidase D [CPD]), which is distinct from the multi-serotype AAV receptor (AAVR). AAVR2 enables the transduction of clade E AAVs, including AAV8, and determines an exclusive AAVR-independent transduction pathway for AAV11 and AAV12. We characterized direct binding between the AAV8 capsid and AAVR2 by cryo-electron microscopy (cryo-EM) and identified contact residues. We observed that AAV8 directly binds to the carboxypeptidase-like domain 1 of AAVR2 via its variable region VIII and demonstrated that AAV capsids that lack AAVR2 binding can be bioengineered to engage with AAVR2. Finally, we overexpressed a minimal functional AAVR2 to enhance AAV transduction in vivo. Our study provides insights into AAV biology and clinically deployable solutions to reduce dose-related toxicities associated with AAV vectors. PubMed: 40664211DOI: 10.1016/j.cell.2025.06.026 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.89 Å) |
Structure validation
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