7yrh

Cryo-EM structure of compact coxsackievirus A16 empty particle in complex with a neutralizing antibody 9B5Cryo-EM structure of compact coxsackievirus A16 empty particle in complex with a neutralizing antibody 9B5

Structural highlights 7yrh is a 5 chain structure with sequence from Coxsackievirus A16. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.35Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function POLG_CX16T Protein VP1: Forms, together with VP2 and VP3, an icosahedral capsid (pseudo T=3), 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome. Protein VP1 mainly forms the vertices of the capsid. VP1 interacts with host cell receptor to provide virion attachment to target cell. After binding to its receptor, the capsid undergoes conformational changes. VP1 N-terminus (that contains an amphipathic alpha-helix) is externalized, VP4 is released and together, they shape a virion-cell connecting channel and a pore in the host membrane through which RNase-protected transfer of the viral genome takes place. After genome has been released, the channel shrinks (By similarity). Protein VP2: Forms, together with VP1 and VP3, an icosahedral capsid (pseudo T=3), 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Protein VP3: Forms, together with VP1 and VP2, an icosahedral capsid (pseudo T=3), 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Protein VP4: Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. VP4 is released, VP1 N-terminus is externalized, and together, they shape a virion-cell connecting channel and a pore in the host membrane through which RNase-protected transfer of the viral genome takes place. After genome has been released, the channel shrinks (By similarity). Protein VP0: Protein VP0: VP0 precursor is a component of immature procapsids, which gives rise to VP4 and VP2 after maturation. Allows the capsid to remain inactive before the maturation step (By similarity). Protease 2A: cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut off the capped cellular mRNA transcription (By similarity). Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity). Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor. It also inhibits endoplasmic reticulum-to-Golgi transport (By similarity). Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity). Publication Abstract from PubMed Coxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working mechanisms of two CVA16-specific neutralizing monoclonal antibodies (MAbs), 9B5 and 8C4, are comprehensively investigated. Both 9B5 and 8C4 display potent neutralization in vitro and prophylactic and therapeutic efficacy in a mouse model of CVA16 infection. Mechanistically, 9B5 exerts neutralization primarily through inhibiting CVA16 attachment to cell surface via blockade of CVA16 binding to its attachment receptor, heparan sulfate, whereas 8C4 functions mainly at the post-attachment stage of CVA16 entry by interfering with the interaction between CVA16 and its uncoating receptor SCARB2. Cryo-EM studies show that 9B5 and 8C4 target distinct epitopes located at the 5-fold and 3-fold protrusions of CVA16 capsids, respectively, and exhibit differential binding preference to three forms of naturally occurring CVA16 particles. Moreover, 9B5 and 8C4 are compatible in formulating an antibody cocktail which displays the ability to prevent virus escape seen with individual MAbs. Together, our work elucidates the functional and structural basis of CVA16 antibody-mediated neutralization and protection, providing important information for design and development of effective CVA16 vaccines and antibody therapies. Molecular mechanism of antibody neutralization of coxsackievirus A16.,Zhang C, Liu C, Shi J, Wang Y, Xu C, Ye X, Liu Q, Li X, Qiao W, Yin Y, Cong Y, Huang Z Nat Commun. 2022 Dec 21;13(1):7854. doi: 10.1038/s41467-022-35575-w. PMID:36543790 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

spinqualitylabelsall models 7yrh, resolution 3.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image