8XCD

Macaca fascicularis NTCP in complex with YN69083 Fab

Summary for 8XCD

• Entry DOI: 10.2210/pdb8xcd/pdb
• EMDB information: 38240
• Descriptor: Solute carrier family 10 member a1, YN69083 Fab Heavy chain, YN69083 Fab Light chain, ... (4 entities in total)
• Functional Keywords: transporter, transport protein-immune system complex, transport protein/immune system
• Biological source: Macaca fascicularis (crab-eating macaque); More
• Total number of polymer chains: 3
• Total formula weight: 90135.48

Authors

Park, J.H.,Ishimoto, N.,Park, S.Y. (deposition date: 2023-12-08, release date: 2024-11-13, Last modification date: 2024-11-27)

Primary citation

Shionoya, K.,Park, J.H.,Ekimoto, T.,Takeuchi, J.S.,Mifune, J.,Morita, T.,Ishimoto, N.,Umezawa, H.,Yamamoto, K.,Kobayashi, C.,Kusunoki, A.,Nomura, N.,Iwata, S.,Muramatsu, M.,Tame, J.R.H.,Ikeguchi, M.,Park, S.Y.,Watashi, K.
Structural basis for hepatitis B virus restriction by a viral receptor homologue.
Nat Commun, 15:9241-9241, 2024

PubMed Abstract: Macaque restricts hepatitis B virus (HBV) infection because its receptor homologue, NTCP (mNTCP), cannot bind preS1 on viral surface. To reveal how mNTCP loses the viral receptor function, we here solve the cryo-electron microscopy structure of mNTCP. Superposing on the human NTCP (hNTCP)-preS1 complex structure shows that Arg158 of mNTCP causes steric clash to prevent preS1 from embedding onto the bile acid tunnel of NTCP. Cell-based mutation analysis confirms that only Gly158 permitted preS1 binding, in contrast to robust bile acid transport among mutations. As the second determinant, Asn86 on the extracellular surface of mNTCP shows less capacity to restrain preS1 from dynamic fluctuation than Lys86 of hNTCP, resulting in unstable preS1 binding. Additionally, presence of long-chain conjugated-bile acids in the tunnel induces steric hindrance with preS1 through their tailed-chain. This study presents structural basis in which multiple sites in mNTCP constitute a molecular barrier to strictly restrict HBV.

PubMed: 39455604
DOI: 10.1038/s41467-024-53533-6

Experimental method

ELECTRON MICROSCOPY (3.49 Å)