Solution structure of the phosphoryl transfer complex between the cytoplasmic A domain of the mannitol transporter IIMannitol and HPr of the Escherichia coli phosphotransferase system

Gabriel Cornilescu, Byeong Ryong Lee, Claudia C. Cornilescu, Guangshun Wang, Alan Peterkofsky, G. Marius Clore

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The solution structure of the complex between the cytoplasmic A domain (IIAMtl) of the mannitol transporter IIMannitol and the histidine-containing phosphocarrier protein (HPr) of the Escherichia coli phosphotransferase system has been solved by NMR, including the use of conjoined rigid body/torsion angle dynamics, and residual dipolar couplings, coupled with cross-validation, to permit accurate orientation of the two proteins. A convex surface on HPr, formed by helices 1 and 2, interacts with a complementary concave depression on the surface of IIAMtl formed by helix 3, portions of helices 2 and 4, and β-strands 2 and 3. The majority of intermolecular contacts are hydrophobic, with a small number of electrostatic interactions at the periphery of the interface. The active site histidines, His-15 of HPr and His-65 of IIAMtl, are in close spatial proximity, and a pentacoordinate phosphoryl transition state can be readily accommodated with no change in protein-protein orientation and only minimal perturbations of the backbone immediately adjacent to the histidines. Comparison with two previously solved structures of complexes of HPr with partner proteins of the phosphotransferase system, the N-terminal domain of enzyme I (EIN) and enzyme IIAGlucose (IIAGlc), reveals a number of common features despite the fact that EIN, IIAGlc, and IIAMtl bear no structural resemblance to one another. Thus, entirely different underlying structural elements can form binding surfaces for HPr that are similar in terms of both shape and residue composition. These structural comparisons illustrate the roles of surface and residue complementarity, redundancy, incremental build-up of specificity and conformational side chain plasticity in the formation of transient specific protein-protein complexes in signal transduction pathways.

Original languageEnglish (US)
Pages (from-to)42289-42298
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number44
DOIs
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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