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|
| Type |
Poster Presentation |
| Area |
Physical Chemistry |
| Room No. |
Event Hall |
| Time |
4월 20일 (금요일) 11:00~12:30 |
| Code |
PHYS.P-87 |
| Subject |
Site-Directed Binding Thermodynamics Analysis of pKID-KIX Complex |
| Authors |
Song-Ho Chong, Sihyun Ham*
Department of Chemistry, Sookmyung Women's University, Korea
|
| Abstract |
Uncovering the molecular details of interactions between intrinsically disordered proteins and their partners is crucial to understand and eventually modify their function in gene regulation and signal transduction. Site-directed mutation is a common technique both in experimental and computational studies for identifying hot spots in protein-protein interactions, but its application sometimes causes undesired significant alternations in protein structures. Here, we apply the site-directed thermodynamic analysis method - a computational approach that does not call for introducing any mutations - to investigate in situ interactions between the disordered pKID region (residues 116-149) of CREB protein and the KIX domain (residues 586-672) of CREB binding protein. We find that interactions between hydrophobic residues that belong to the alpha_B helix of pKID and the alpha_3 helix of KIX play a dominant role in determining the binding affinity. In particular, Ile-137 and Tyr-134 are found to be the most and the second most significant residues, respectively, in pKID, and Tyr-658 and Ala-654 are the corresponding residues in KIX, which is in accord with the experimental observation. We also show that positively charged residues in the alpha_A helix of pKID and negatively charged residues in the alpha_3 helix of KIX provide weak but specific interactions between pKID and KIX. The difference in strength of the two types of interactions explains the experimentally observed sequence of events in which the alpha_B helix of pKID binds first to KIX followed by the binding of the alpha_A helix. |
| E-mail |
songho.chong@gmail.com |
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121st General Meeting of the KCS