4NBP

Crystal structure of the JCV large T-antigen origin binding domain

Summary for 4NBP

• Entry DOI: 10.2210/pdb4nbp/pdb
• Related: 4LIF 4LMD
• Descriptor: Large T antigen, L(+)-TARTARIC ACID (3 entities in total)
• Functional Keywords: origin binding domain, dna replication, binds dna, hydrolase
• Biological source: JC polyomavirus (JCPyV)
• Cellular location: Host nucleus (By similarity): P03072
• Total number of polymer chains: 1
• Total formula weight: 15470.56

Authors

Meinke, G.,Bohm, A.,Bullock, P. (deposition date: 2013-10-23, release date: 2014-03-05, Last modification date: 2024-10-30)

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

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: 24586168
DOI: 10.1371/journal.ppat.1003966

Experimental method

X-RAY DIFFRACTION (1.315 Å)