3tn9 | pdb_00003tn9
X-ray structure of the HRV2 empty capsid (B-particle)
Structural highlights
FunctionPOLG_HRV2 Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with human VLDLR to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm.[1] [2] VP0 precursor is a component of immature procapsids (By similarity).[3] [4] Protein 2A is a 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 down the capped cellular mRNA transcription.[5] [6] Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).[7] [8] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[9] [10] Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).[11] [12] Protein 3C is a 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 co-operatively to the protease (By similarity).[13] [14] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[15] [16] Publication Abstract from PubMedUpon attachment to their respective receptor, human rhinoviruses (HRVs) are internalized into the host cell via different pathways but undergo similar structural changes. This ultimately results in the delivery of the viral RNA into the cytoplasm for replication. To improve our understanding of the conformational modifications associated with the release of the viral genome, we have determined the X-ray structure at 3.0 A resolution of the end-stage of HRV2 uncoating, the empty capsid. The structure shows important conformational changes in the capsid protomer. In particular, a hinge movement around the hydrophobic pocket of VP1 allows a coordinated shift of VP2 and VP3. This overall displacement forces a reorganization of the inter-protomer interfaces, resulting in a particle expansion and in the opening of new channels in the capsid core. These new breaches in the capsid, opening one at the base of the canyon and the second at the particle two-fold axes, might act as gates for the externalization of the VP1 N-terminus and the extrusion of the viral RNA, respectively. The structural comparison between native and empty HRV2 particles unveils a number of pH-sensitive amino acid residues, conserved in rhinoviruses, which participate in the structural rearrangements involved in the uncoating process. Insights into minor group rhinovirus uncoating: the X-ray structure of the HRV2 empty capsid.,Garriga D, Pickl-Herk A, Luque D, Wruss J, Caston JR, Blaas D, Verdaguer N PLoS Pathog. 2012 Jan;8(1):e1002473. Epub 2012 Jan 5. PMID:22241997[17] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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