2m1s
NMR assignment of the arenaviral protein Z from Lassa fever virus
Structural highlights
FunctionZ_LASSJ Plays a crucial role in virion assembly and budding. Expressed late in the virus life cycle, it acts as an inhibitor of viral transcription and RNA synthesis by interacting with the viral polymerase L (By similarity). Presumably recruits the NP encapsidated genome to cellular membranes at budding sites via direct interaction with NP. Plays critical roles in the final steps of viral release by interacting with host TSG101, a member of the vacuolar protein-sorting pathway and using other cellular host proteins involved in vesicle formation pathway. The budding of the virus progeny occurs after association of protein Z with the viral glycoprotein complex SSP-GP1-GP2 at the cell periphery, step that requires myristoylation of protein Z. Also selectively represses protein production by associating with host eIF4E.[1] [2] Publication Abstract from PubMedThe eukaryotic translation initiation factor eIF4E, a potent oncogene, is highly regulated. One class of eIF4E regulators, including eIF4G and the 4E-binding proteins (4E-BPs), interact with eIF4E using a conserved YXXXXLPhi-binding site. The structural basis of this interaction and its regulation are well established. Really Interesting New Gene (RING) domain containing proteins, such as the promyelocytic leukemia protein PML and the arenaviral protein Z, represent a second class of eIF4E regulators that inhibit eIF4E function by decreasing eIF4E's affinity for its m(7)G cap ligand. To elucidate the structural basis of this inhibition, we determined the structure of Z and studied the Z-eIF4E complex using NMR methods. We show that Z interacts with eIF4E via a novel binding site, which has no homology with that of eIF4G or the 4E-BPs, and is different from the RING recognition site used in the ubiquitin system. Z and eIF4G interact with distinct parts of eIF4E and differentially alter the conformation of the m(7)G cap-binding site. Our results provide a molecular basis for how PML and Z RINGs reduce the affinity of eIF4E for the m(7)G cap and thereby act as key inhibitors of eIF4E function. Furthermore, our findings provide unique insights into RING protein interactions. Structural characterization of the Z RING-eIF4E complex reveals a distinct mode of control for eIF4E.,Volpon L, Osborne MJ, Capul AA, de la Torre JC, Borden KL Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5441-6. Epub 2010 Mar 8. PMID:20212144[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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