1ik7

Crystal Structure of the Uncomplexed Pelle Death Domain

spinqualitylabelsall models 1ik7, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ik7 is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MPD, TRS Related: 1d2z Gene: pelle (Drosophila melanogaster) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The death domain (DD) of the protein kinase Pelle adopts a six-helix bundle fold in the crystal structure of the complex with its dimerization partner, Tube-DD. However, in crystals obtained from a solution of 45% 2-methyl-2,4-pentanediol (MPD), the C-terminal half of Pelle-DD folds into a single helix, and the N-terminal half of the molecule is disordered. The helical segment forms an antiparallel dimer with the corresponding helix of a symmetry-related molecule, and together they form extensive lattice interactions similar in number, composition, and buried surface to those in the six-helix bundle of the native fold. Secondary structure analysis by heteronuclear nuclear magnetic resonance spectroscopy (NMR) demonstrates that Pelle-DD adopts a six-helix bundle fold in aqueous solution. The fold is perturbed by MPD, with the largest chemical shift changes in one helix and two loop regions that encompass the Tube-DD binding site. Pelle-DD is stable to urea denaturation with a folding free energy of 7.9 kcal/mol at 25 degrees C but is destabilized, with loss of urea binding sites, in the presence of MPD. The data are consistent with a cosolvent denaturation model in which MPD denatures the N terminus of Pelle-DD but induces the C terminus to form a more compact structure and aggregate. A similar perturbation in vivo might occur at the plasma membrane and could have consequences for Pelle-mediated regulation. Generally, crystallographers should be aware that high concentrations of MPD or related cosolvents can alter the tertiary structure of susceptible proteins. Cosolvent-induced transformation of a death domain tertiary structure.,Xiao T, Gardner KH, Sprang SR Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11151-6. Epub 2002 Aug 12. PMID:12177432 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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