5yax

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Crystal structure of a human neutralizing antibody bound to a HBV preS1 peptide

Structural highlights

5yax is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:NA
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[B2CXZ0_HBV] The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches the virus to cell receptors and thereby initiating infection. This interaction determines the species specificity and liver tropism. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis. The large envelope protein also assures fusion between virion membrane and endosomal membrane. In its internal conformation the protein plays a role in virion morphogenesis and mediates the contact with the nucleocapsid like a matrix protein.[SAAS:SAAS00857669] The middle envelope protein plays an important role in the budding of the virion. It is involved in the induction of budding in a nucleocapsid independent way. In this process the majority of envelope proteins bud to form subviral lipoprotein particles of 22 nm of diameter that do not contain a nucleocapsid.[SAAS:SAAS00796594]

Publication Abstract from PubMed

Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects. It also acts therapeutically by eliciting antibody-Fc-dependent immunological effector functions that impose durable suppression of viral infection in HBV-infected mice, resulting in reductions in the levels of the small envelope antigen and viral DNA, with no emergence of escape mutants. Our results illustrate a novel antibody-Fc-dependent approach for HBV treatment and suggest 2H5-A14 as a novel clinical candidate for HBV prevention and treatment of chronic HBV infection.

A potent human neutralizing antibody Fc-dependently reduces established HBV infections.,Li D, He W, Liu X, Zheng S, Qi Y, Li H, Mao F, Liu J, Sun Y, Pan L, Du K, Ye K, Li W, Sui J Elife. 2017 Sep 26;6. pii: e26738. doi: 10.7554/eLife.26738. PMID:28949917[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
16 reviews cite this structure
Immunobiology and pathogenesis of hepatitis B virus infection.
Iannacone et al. (2022)
15 more
40 other articles
No citations found

See Also

References

  1. ↑ Li D, He W, Liu X, Zheng S, Qi Y, Li H, Mao F, Liu J, Sun Y, Pan L, Du K, Ye K, Li W, Sui J. A potent human neutralizing antibody Fc-dependently reduces established HBV infections. Elife. 2017 Sep 26;6. pii: e26738. doi: 10.7554/eLife.26738. PMID:28949917 doi:http://dx.doi.org/10.7554/eLife.26738

Contents


PDB ID 5yax

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OCA

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