Mapping Native Peptide–Peptide Noncovalent Interactions: Insights from Trapped Ion Mobility Spectrometry, Electron- and UV-Fragmentation, Tandem Mass Spectrometry, and Molecular Dynamics

Le résumé fourni par la source

Noncovalent interactions play an important role in the way protein structures and protein-protein interactions are stabilized. Mapping these interactions at a molecular level is crucial as peptide complexes serve as models for protein-protein interfaces. In this work, complementary analyses using trapped ion mobility spectrometry (TIMS), tandem ECD/UVPD MS fragmentation, and molecular dynamics were applied to the study of native peptide-peptide complexes. In particular, three complexes representing peptide-peptide intramolecular interactions of the intrinsically disordered high-mobility group AT-Hook2 (HMGA2) protein were described. AT-hook peptides, when complexed with the C-terminal tail (CTMP), showed a higher gas-phase stability for ATHP1-CTMP, followed by ATHP2-CTMP and ATHP3-CTMP. High sequence coverage was obtained by using ECD and UVPD fragmentation for the single peptides (∼100%) and the peptide-peptide complexes (∼75%). At least three peptide-peptide structures were separated in the mobility domain for the ATHP-CTMP complexes. All three complexes showed high structural diversity and the possibility of being aligned in forward and backward orientations.

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