5a76

KSHV LANA (ORF73) C-terminal domain, open non-ring conformation: orthorhombic crystal form

spinqualitylabelsall models 5a76, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5a76 is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Latency-associated nuclear antigen (LANA) is central to episomal tethering, replication and transcriptional regulation of gamma2-herpesviruses. LANA binds cooperatively to the terminal repeat (TR) region of the viral episome via adjacent LANA binding sites (LBS), but the molecular mechanism by which LANA assembles on the TR remains elusive. We show that KSHV LANA and MHV-68 LANA proteins bind LBS DNA using strikingly different modes. Solution structure of LANA complexes revealed that while kLANA tetramer is intrinsically bent both in the free and bound state to LBS1-2 DNA, mLANA oligomers instead adopt a rigid linear conformation. In addition, we report a novel non-ring kLANA structure that displays more flexibility at its assembly interface than previously demonstrated. We identified a hydrophobic pivot point located at the dimer-dimer assembly interface, which gives rotational freedom for kLANA to adopt variable conformations to accommodate both LBS1-2 and LBS2-1-3 DNA. Alterations in the arrangement of LBS within TR or at the tetramer assembly interface have a drastic effect on the ability of kLANA binding. We also show kLANA and mLANA DNA binding functions can be reciprocated. Although KSHV and MHV-68 are closely related, the findings provide new insights into how the structure, oligomerization, and DNA binding of LANA have evolved differently to assemble on the TR DNA. KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA.,Ponnusamy R, Petoukhov MV, Correia B, Custodio TF, Juillard F, Tan M, Pires de Miranda M, Carrondo MA, Simas JP, Kaye KM, Svergun DI, McVey CE Nucleic Acids Res. 2015 Nov 16;43(20):10039-54. doi: 10.1093/nar/gkv987. Epub, 2015 Sep 30. PMID:26424851 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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