TY - JOUR
T1 - High-definition NMR structure of PED/PEA-15 death effector domain reveals details of key polar side chain interactions
AU - Twomey, Edward C.
AU - Wei, Yufeng
N1 - Funding Information:
We thank Dr. Justine Hill and Yu Wei for cloning, expression, and labeling of PED/PEA-15 protein, and Dr. Justine Hill for providing 1N3K NMR restraints. We are grateful for various funding and fellowships from Seton Hall University Research Council , the Celgene Corporation , Eric F. Ross Research Fellowship, and New Jersey Space Grant Consortium/NASA .
PY - 2012/7/20
Y1 - 2012/7/20
N2 - Death effector domain (DED) proteins constitute a subfamily of the large death domain superfamily that is primarily involved in apoptosis pathways. DED structures have characteristic side chain-side chain interactions among polar residues on the protein surface, forming a network of hydrogen bonds and salt bridges. The polar interaction network is functionally important in promoting protein-protein interactions by maintaining optimal side chain orientations. We have refined the solution DED structure of the PED/PEA-15 protein, a representative member of DED subfamily, using traditional NMR restraints with the addition of residual dipolar coupling (RDC) restraints from two independent alignment media, and employed the explicit solvent refinement protocol. The newly refined DED structure of PED/PEA-15 possesses higher structural quality as indicated by WHAT IF Z-scores, with most significant improvement in the backbone conformation normality quality factor. This higher quality DED structure of PED/PEA-15 leads to the identification of a number of key polar side chain interactions, which are not typically observed in NMR protein structures. The elucidation of polar side chain interactions is a key step towards the understanding of protein-protein interactions involving the death domain superfamily. The NMR structures with extensive details of protein structural features are thereby termed high-definition (HD) NMR structures.
AB - Death effector domain (DED) proteins constitute a subfamily of the large death domain superfamily that is primarily involved in apoptosis pathways. DED structures have characteristic side chain-side chain interactions among polar residues on the protein surface, forming a network of hydrogen bonds and salt bridges. The polar interaction network is functionally important in promoting protein-protein interactions by maintaining optimal side chain orientations. We have refined the solution DED structure of the PED/PEA-15 protein, a representative member of DED subfamily, using traditional NMR restraints with the addition of residual dipolar coupling (RDC) restraints from two independent alignment media, and employed the explicit solvent refinement protocol. The newly refined DED structure of PED/PEA-15 possesses higher structural quality as indicated by WHAT IF Z-scores, with most significant improvement in the backbone conformation normality quality factor. This higher quality DED structure of PED/PEA-15 leads to the identification of a number of key polar side chain interactions, which are not typically observed in NMR protein structures. The elucidation of polar side chain interactions is a key step towards the understanding of protein-protein interactions involving the death domain superfamily. The NMR structures with extensive details of protein structural features are thereby termed high-definition (HD) NMR structures.
KW - Polar interactions
KW - Protein structure
KW - Protein-protein interactions
KW - Structure determination
KW - Structure validation
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U2 - 10.1016/j.bbrc.2012.06.091
DO - 10.1016/j.bbrc.2012.06.091
M3 - Article
C2 - 22732408
AN - SCOPUS:84864103948
SN - 0006-291X
VL - 424
SP - 141
EP - 146
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -