9VZP
Human FATP2 in complex with oleic acid and oleoyl-AMP in intermediate state
This is a non-PDB format compatible entry.
Summary for 9VZP
| Entry DOI | 10.2210/pdb9vzp/pdb |
| EMDB information | 65482 |
| Descriptor | Long-chain fatty acid transport protein 2, MAGNESIUM ION, [[(2~{R},3~{S},4~{S},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] (~{Z})-octadec-9-enoate, ... (4 entities in total) |
| Functional Keywords | a membrane protein with ligands, protein transport |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 71323.60 |
| Authors | |
| Primary citation | Li, A.,Shi, J.,Xu, X.,Yang, Y.,Feng, S.,Ma, D. Structural basis of fatty acid activation and transport by human FATP2. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Fatty acid transport proteins (FATPs) are responsible for efficient uptake of fatty acids (FAs), essential biomolecules that play critical roles in development and growth. However, the lack of three-dimensional structures of FATPs has hindered our understanding of their mechanisms. Here, we report two cryo-EM structures of human FATP2a: wild-type (WT) FATP2a in intermediate state at 2.93 Å and a catalytic mutant of FATP2a in pre-catalytic state at 2.76 Å. In the two structures, both the oleoyl-AMP intermediate and ATP occupy the same central pocket with the acyl group of oleoyl-AMP pointing upwards and placed in a hydrophobic tunnel while the phosphate groups of ATP pointing downwards and interacting with a central loop. The structures also reveal that FAs from the membrane must undergo a two-step translocation to access the catalytic center. The binding of a new FA before the completion of a working cycle may be crucial to ensure the catalytic and transport efficiency. Furthermore, we demonstrate that FATP2a transport FAs, strictly dependent on the activation of FAs through the acyl-CoA synthetase activity. Our findings provide important insights into the working mechanism of FATPs and offer a structural basis for the development of inhibitors targeting FATPs to treat related diseases. PubMed: 42722660DOI: 10.1038/s41467-026-76658-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.93 Å) |
Structure validation
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