Structural highlights
Function
ABCB9_MOUSE ATP-dependent low-affinity peptide transporter which translocates a broad spectrum of peptides from the cytosol to the lysosomal lumen for degradation. Displays a broad peptide length specificity from 6-mer up to at least 59-mer peptides with an optimum of 23-mers. Binds and transports smaller and larger peptides with the same affinity. Favors positively charged, aromatic or hydrophobic residues in the N- and C-terminal positions whereas negatively charged residues as well as asparagine and methionine are not favored.[UniProtKB:Q9NP78]
Publication Abstract from PubMed
TAPL is a lysosomal ATP-binding cassette transporter that translocates a broad spectrum of polypeptides from the cytoplasm into the lysosomal lumen. Here we report that, in addition to its well-known role as a peptide translocator, TAPL exhibits an ATP-dependent phosphatidylserine floppase activity that is the possible cause of its high basal ATPase activity and of the lack of coupling between ATP hydrolysis and peptide efflux. We also present the cryo-EM structures of mouse TAPL complexed with (i) phospholipid, (ii) cholesteryl hemisuccinate (CHS) and 9-mer peptide, and (iii) ADP.BeF3. The inward-facing structure reveals that F449 protrudes into the cylindrical transport pathway and divides it into a large hydrophilic central cavity and a sizable hydrophobic upper cavity. In the structure, the peptide binds to TAPL in horizontally-stretched fashion within the central cavity, while lipid molecules plug vertically into the upper cavity. Together, our results suggest that TAPL uses different mechanisms to function as a peptide translocase and a phosphatidylserine floppase.
The lysosomal transporter TAPL has a dual role as peptide translocator and phosphatidylserine floppase.,Park JG, Kim S, Jang E, Choi SH, Han H, Ju S, Kim JW, Min DS, Jin MS Nat Commun. 2022 Oct 4;13(1):5851. doi: 10.1038/s41467-022-33593-2. PMID:36195619[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Park JG, Kim S, Jang E, Choi SH, Han H, Ju S, Kim JW, Min DS, Jin MS. The lysosomal transporter TAPL has a dual role as peptide translocator and phosphatidylserine floppase. Nat Commun. 2022 Oct 4;13(1):5851. doi: 10.1038/s41467-022-33593-2. PMID:36195619 doi:http://dx.doi.org/10.1038/s41467-022-33593-2
