Journal
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
Volume 30, Issue 1, Pages 94-102Publisher
AMER CHEMICAL SOC
DOI: 10.1007/s13361-018-2043-6
Keywords
Transcriptional coactivator; Protein:protein interaction; Inhibitor; Ion mobility; Native mass spectrometry
Funding
- National Science Foundation (CAREER) [1253384]
- NIH [F31GM113561, 3RO1 GM65530]
- Direct For Mathematical & Physical Scien [1253384] Funding Source: National Science Foundation
- Division Of Chemistry [1253384] Funding Source: National Science Foundation
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The kinase-inducible domain (KIX) of the transcriptional coactivator CBP binds multiple transcriptional regulators through two allosterically connected sites. Establishing a method for observing activator-specific KIX conformations would facilitate the discovery of drug-like molecules that capture specific conformations and further elucidate how distinct activator-KIX complexes produce differential transcriptional effects. However, the transient and low to moderate affinity interactions between activators and KIX are difficult to capture using traditional biophysical assays. Here, we describe a collision-induced unfolding-based approach that produces unique fingerprints for peptides bound to each of the two available sites within KIX, as well as a third fingerprint for ternary KIX complexes. Furthermore, we evaluate the analytical utility of unfolding fingerprints for KIX complexes using CIUSuite, and conclude by speculating as to the structural origins of the conformational families created from KIX:peptide complexes following collisional activation.
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