4LIF
Crystal structure of the JCV large T-antigen origin binding domain
Summary for 4LIF
| Entry DOI | 10.2210/pdb4lif/pdb |
| Related | 4LMD 4NBP |
| Descriptor | Large T antigen, SULFATE ION (3 entities in total) |
| Functional Keywords | origin binding domain, replication, polyomavirus, hydrolase, dna binding protein |
| Biological source | JC polyomavirus (JCPyV) |
| Cellular location | Host nucleus (By similarity): P03072 |
| Total number of polymer chains | 1 |
| Total formula weight | 15362.52 |
| Authors | Meinke, G.,Bohm, A.,Bullock, P. (deposition date: 2013-07-02, release date: 2014-03-05, Last modification date: 2023-09-20) |
| Primary citation | Meinke, G.,Phelan, P.J.,Kalekar, R.,Shin, J.,Archambault, J.,Bohm, A.,Bullock, P.A. Insights into the Initiation of JC Virus DNA Replication Derived from the Crystal Structure of the T-Antigen Origin Binding Domain. Plos Pathog., 10:e1003966-e1003966, 2014 Cited by PubMed Abstract: JC virus is a member of the Polyomavirus family of DNA tumor viruses and the causative agent of progressive multifocal leukoencephalopathy (PML). PML is a disease that occurs primarily in people who are immunocompromised and is usually fatal. As with other Polyomavirus family members, the replication of JC virus (JCV) DNA is dependent upon the virally encoded protein T-antigen. To further our understanding of JCV replication, we have determined the crystal structure of the origin-binding domain (OBD) of JCV T-antigen. This structure provides the first molecular understanding of JCV T-ag replication functions; for example, it suggests how the JCV T-ag OBD site-specifically binds to the major groove of GAGGC sequences in the origin. Furthermore, these studies suggest how the JCV OBDs interact during subsequent oligomerization events. We also report that the OBD contains a novel "pocket"; which sequesters the A1 & B2 loops of neighboring molecules. Mutagenesis of a residue in the pocket associated with the JCV T-ag OBD interfered with viral replication. Finally, we report that relative to the SV40 OBD, the surface of the JCV OBD contains one hemisphere that is highly conserved and one that is highly variable. PubMed: 24586168DOI: 10.1371/journal.ppat.1003966 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
Download full validation report
