Small-world network approach to identify key residues in protein-protein interaction

2004 ◽  
Vol 58 (3) ◽  
pp. 672-682 ◽  
Author(s):  
Antonio del Sol ◽  
Paul O'Meara
Keyword(s):  
Protein Interaction ◽  
Small World ◽  
Small World Network ◽  
Network Approach ◽  
Protein Protein Interaction ◽  
Key Residues

scholarly journals Nonnatural protein-protein interaction-pair design by key residues grafting

2007 ◽  
Vol 104 (13) ◽  
pp. 5330-5335 ◽  
Author(s):  
S. Liu ◽  
S. Liu ◽  
X. Zhu ◽  
H. Liang ◽  
A. Cao ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Protein Protein Interaction ◽  
Key Residues ◽  
Protein Interaction Pair

Discovery and identification of Cdc37-derived peptides targeting the Hsp90–Cdc37 protein–protein interaction

RSC Advances ◽  
2015 ◽  
Vol 5 (116) ◽  
pp. 96138-96145 ◽  
Author(s):  
Lei Wang ◽  
Qi-Chao Bao ◽  
Xiao-Li Xu ◽  
Fen Jiang ◽  
Kai Gu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Protein Interaction ◽  
Peptide Inhibitors ◽  
Dynamics Simulation ◽  
Protein Protein Interaction ◽  
Binding Interface ◽  
Combined Strategy ◽  
Key Residues

In order to explore the key residues of the Hsp90–Cdc37 binding interface for further design of peptide inhibitors, a combined strategy of molecular dynamics simulation and MM-PBSA analysis was performed.

Apoptosis-associated tyrosine kinase scaffolding of protein phosphatase 1 and SPAK reveals a novel pathway for Na-K-2C1 cotransporter regulation

2007 ◽  
Vol 292 (5) ◽  
pp. C1809-C1815 ◽  
Author(s):  
Kenneth B. E. Gagnon ◽  
Roger England ◽  
Lisa Diehl ◽  
Eric Delpire
Keyword(s):  
Xenopus Laevis ◽  
Tyrosine Kinase ◽  
Protein Interaction ◽  
Protein Phosphatase ◽  
Catalytic Domain ◽  
Protein Phosphatase 1 ◽  
Xenopus Laevis Oocytes ◽  
Physical Interaction ◽  
Protein Protein Interaction ◽  
Key Residues

Previous work from our laboratory and others has established that Ste-20-related proline-alanine-rich kinase (SPAK/PASK) is central to the regulation of NKCC1 function. With no lysine (K) kinase (WNK4) has also been implicated in the regulation of NKCC1 activity through upstream activation of SPAK. Because previous studies from our laboratory also demonstrated a protein-protein interaction between SPAK and apoptosis-associated tyrosine kinase (AATYK), we explore here the possibility that AATYK is another component of the regulation of NKCC1. Heterologous expression of AATYK1 in NKCC1-injected Xenopus laevis oocytes markedly inhibited cotransporter activity under isosmotic conditions. Interestingly, mutation of key residues in the catalytic domain of AATYK1 revealed that the kinase activity does not play a role in the suppression of NKCC1 function. However, mutagenesis of the two SPAK-binding motifs in AATYK1 completely abrogated this effect. As protein phosphatase 1 (PP1) also plays a central role in the dephosphorylation and inactivation of NKCC1, we investigated the possibility that AATYK1 interacts with the phosphatase. We identified a PP1 docking motif in AATYK1 and demonstrated interaction using yeast-2-hybrid analysis. Mutation of a key valine residue (V1175) within this motif prevented protein-protein interaction. Furthermore, the physical interaction between PP1 and AATYK was required for inhibition of NKCC1 activity in Xenopus laevis oocytes. Taken together, our data are consistent with AATYK1 indirectly inhibiting the SPAK/WNK4 activation of the cotransporter by scaffolding an inhibitory phosphatase in proximity to a stimulatory kinase.

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