Solution structure and phosphopeptide binding to the N-terminal domain of Yersinia YopH: comparison with a crystal structure.
Virulence of pathogenic bacteria of the genus Yersinia requires the injection of six effector proteins into the cytoplasm of host cells. The amino-terminal domain of one of these effectors, the tyrosine phosphatase YopH, is essential for translocation of YopH, as well as for targeting it to phosphotyrosine-containing substrates of the type pYxxP. We report the high-resolution solution structure of the N-terminal domain (residues 1-129) from the Yersinia pseudotuberculosis YopH (YopH-NT) in complex with N-acetyl-DEpYDDPF-NH(2), a peptide derived from an in vivo protein substrate. In contrast to the domain-swapped dimer observed in a crystal structure of the same protein (Smith, C. L., Khandelwal, P., Keliikuli, K., Zuiderweg, E. R. P., and Saper, M. A. (2001) Mol. Microbiol. 42, 967-979), YopH-NT is monomeric in solution. The peptide binding site is located on a beta-hairpin that becomes the crossover point in the dimer structure. The binding site has several characteristics that are reminiscent of SH2 domains, which also bind to pYxxP sequences.
Khandelwal
Purnima
P
Biophysics Research Division, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.
Keliikuli
Kai
K
Smith
Craig L
CL
Saper
Mark A
MA
Zuiderweg
Erik R P
ER
D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010743:Phospholipids / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000378:metabolism*; D012996:Solutions; D015011:Yersinia pseudotuberculosis / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; D010743:Phospholipids; D012996:Solutions; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia