9JBM
P5A-ATPase ATP13A1 reconstructed in nanodiscs
Summary for 9JBM
| Entry DOI | 10.2210/pdb9jbm/pdb |
| EMDB information | 61319 |
| Descriptor | Endoplasmic reticulum transmembrane helix translocase, Putative endogenous substrate (2 entities in total) |
| Functional Keywords | er membrane, transmembrane helices, translocation, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 130972.99 |
| Authors | |
| Primary citation | Yang, X.,Li, Y.,Yang, C.,Li, T.,Fang, Z.,Feng, Z.,Liao, J.,Zou, Y. ATP13A1 engages SEC61 to facilitate substrate-specific translocation. Sci Adv, 11:eadt1346-eadt1346, 2025 Cited by PubMed Abstract: The accurate targeting of proteins to their designated cellular compartments is essential for maintaining proper cellular architecture and function. However, interpreting and sorting the highly variable targeting sequences in secreted and membrane proteins present a substantial challenge for achieving precise localization within the secretory pathway. In this study, we demonstrate that atypical signal sequences, characterized by high hydrophobicity and/or the absence of characteristic charges, are recognized by the signal recognition particle and targeted to the endoplasmic reticulum in a reverse orientation. These misoriented signal sequences are subsequently dislocated by the P5A-ATPase ATP13A1 and delivered to SEC61 for further translocation. Using cryo-electron microscopy, we determined the structures of human ATP13A1 in multiple conformations (3.40- to 3.87-angstrom resolution), revealing key residues within its substrate-binding pocket that engage signal sequences through polar interactions. Collectively, our findings elucidate a comprehensive, substrate-specific translocation pathway that ensures both high efficiency and fidelity in protein subcellular localization. PubMed: 40498833DOI: 10.1126/sciadv.adt1346 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.83 Å) |
Structure validation
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