biostudies-literatureBacot-Davis VRNCRR NIH HHSNIAID NIH HHSNIGMS NIH HHS15792-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC4226078biostudies-literatureUnknown111(44)Cardiovirus Leader (L) proteins induce potent antihost inhibition of active cellular nucleocytoplasmic trafficking by triggering aberrant hyperphosphorylation of nuclear pore proteins (Nup). To achieve this, L binds protein RanGTPase (Ran), a key trafficking regulator, and diverts it into tertiary or quaternary complexes with required kinases. The activity of L is regulated by two phosphorylation events not required for Ran binding. Matched NMR studies on the unphosphorylated, singly, and doubly phosphorylated variants of Mengovirus L (L(M)) show both modifications act together to partially stabilize a short internal α-helix comprising L(M) residues 43-46. This motif implies that ionic and Van der Waals forces contributed by phosphorylation help organize downstream residues 48-67 into a neProceedings of the National Academy of Sciences of the United States of AmericaSolution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase.PMC4226078P41GM66326S10RR025062P41 GM066326R56 AI017331S10 RR023438S10RR029220T32 AI078985T32 GM007215P41 RR002301S10 RR029220S10RR023438S10 RR025062S10 RR008438S10 RR002781R01 AI017331P41RR02301Ciomperlik JJCornilescu CCPalmenberg ACBacot-Davis VRBasta HAfalseSolution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase.Cardiovirus Leader (L) proteins induce potent antihost inhibition of active cellular nucleocytoplasmic trafficking by triggering aberrant hyperphosphorylation of nuclear pore proteins (Nup). To achieve this, L binds protein RanGTPase (Ran), a key trafficking regulator, and diverts it into tertiary or quaternary complexes with required kinases. The activity of L is regulated by two phosphorylation events not required for Ran binding. Matched NMR studies on the unphosphorylated, singly, and doubly phosphorylated variants of Mengovirus L (L(M)) show both modifications act together to partially stabilize a short internal α-helix comprising L(M) residues 43-46. This motif implies that ionic and Van der Waals forces contributed by phosphorylation help organize downstream residues 48-67 into a ne2014-01-01T00:00:00Z2014 Nov2026-05-03T22:37:25.897Z2019-03-27T01:39:14ZS-EPMC42260782533186610.1073/pnas.1411098111