PDBsum entry 2mml

Viral protein

PDB id: 2mml

Contents

Protein chain

71 a.a.

Metals

_ZN

PDB id:

2mml

Name:

Viral protein

Title:

T47 phosphorylation of the mengovirus leader protein: nmr studies of the phosphorylation of the mengovirus leader protein reveal stabilization of intermolecular domain interactions

Structure:

Leader protein. Chain: a. Fragment: unp residues 1-67. Engineered: yes

Source:

Mengo virus. Organism_taxid: 12107. Strain: emcv. Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

10 models

Authors:

V.R.Bacot-Davis,F.W.Porter,A.C.Palmenberg

Key ref:

V.R.Bacot-Davis et al. (2014). Solution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase. Proc Natl Acad Sci U S A, 111, 15792-15797. PubMed id: 25331866 DOI: 10.1073/pnas.1411098111

Date:

15-Mar-14 Release date: 15-Oct-14

Protein chain

P12296  (POLG_ENMGO) -  Genome polyprotein from Mengo encephalomyocarditis virus

Seq: 2293 a.a.

Struc: 71 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 2: E.C.3.4.22.28 - picornain 3C.
• Reaction: Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
• Enzyme class 3: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1073/pnas.1411098111

Proc Natl Acad Sci U S A 111:15792-15797 (2014)

PubMed id: 25331866

Solution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase.

V.R.Bacot-Davis, J.J.Ciomperlik, H.A.Basta, C.C.Cornilescu, A.C.Palmenberg.

ABSTRACT

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 (LM) show both modifications act together to partially stabilize a short internal α-helix comprising LM residues 43-46. This motif implies that ionic and Van der Waals forces contributed by phosphorylation help organize downstream residues 48-67 into a new interface. The full structure of LM as bound to Ran (unlabeled) and Ran (216 aa) as bound by LM (unlabeled) places LM into the BP1 binding site of Ran, wrapped by the conformational flexible COOH tail. The arrangement explains the tight KD for this complex and places the LM zinc finger and phosphorylation interface as surface exposed and available for subsequent reactions. The core structure of Ran, outside the COOH tail, is not altered by LM binding and remains accessible for canonical RanGTP partner interactions. Pull-down assays identify at least one putative Ran:LM partner as an exportin, Crm1, or CAS. A model of Ran:LM:Crm1, based on the new structures suggests LM phosphorylation status may mediate Ran's selection of exportin(s) and cargo(s), perverting these native trafficking elements into the lethal antihost Nup phosphorylation pathways.