9IRC

CyroEM structure of hSLC15A4+TASL+Fab235

Summary for 9IRC

• Entry DOI: 10.2210/pdb9irc/pdb
• EMDB information: 60809
• Descriptor: Solute carrier family 15 member 4, TLR adapter interacting with SLC15A4 on the lysosome, Fab235 heavy chain, ... (4 entities in total)
• Functional Keywords: hslc15a4+tasl+fab235 complex, membrane protein, antibody, membrane protein/immune system, membrane protein-immune system complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 109191.45

Authors

Zhu, Y.L.,Zhang, Q.X.,Gao, P. (deposition date: 2024-07-15, release date: 2025-08-20)

Primary citation

Zhu, Y.,Zhang, X.,Zhang, Q.,Sun, P.,Liu, K.,Nie, X.,Ma, J.,Zhang, L.,Gao, Y.,Wang, Y.,Liu, S.,Gao, A.,Zhang, L.,Gao, P.
Development of conformation-selective antibodies targeting human SLC15A4.
Nat Commun, 16:7324-7324, 2025

PubMed Abstract: SLC15A4, an endolysosomal solute carrier family transporter, plays a critical role in TLR7/8/9-induced immune responses through assembling a complex with the downstream adaptor TASL in a conformation-dependent manner. Despite its close functional association and promising therapeutic potential in infections, tumors, and autoimmune diseases, the development of conformation-specific antibodies for human SLC15A4 (hSLC15A4) remains challenging. Here, using a systematic screening and validation approach, we identify a pair of conformation-selective antibodies, clones 107 and 235, targeting the endolysosomal lumen surface of hSLC15A4 with opposite conformation-regulatory activities. Specifically, clone 107 selectively binds to hSLC15A4 in a TASL binding-incompetent luminal-open state; whereas clone 235 stabilizes hSLC15A4 in a TASL binding-competent cytoplasmic-open state. Our research identifies antibodies that recognize distinct conformations of hSLC15A4, potentially enabling modulation of the TLR7/8/9 pathway and contributing to the development of targeted therapies and research tools selectively targeting hSLC15A4.

PubMed: 40781080
DOI: 10.1038/s41467-025-62759-x

Experimental method

ELECTRON MICROSCOPY (2.82 Å)