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Native Nanoproteomics Captures Structure and Dynamics of Endogenous Protein Complexes in Human Heart Tissue

ABSTRACT: To obtain a molecular-level understanding of biological processes, it is critical to perform structural characterization of protein complexes and their subunits directly from human tissues. Native top-down mass spectrometry (MS) has emerged as a complementary technique to traditional structural biology methods. Nonetheless, native top-down MS has primarily characterized recombinant or high-abundance protein complexes, as strategies to enrich and preserve low-abundance protein complexes from human tissues is lacking. Here we have developed a native nanoproteomics platform integrating peptide-functionalized nanoparticles to characterize low-abundance protein complexes with high-resolution native top-down MS. We then apply our native nanoproteomics strategy to enrich and structurally elucidate endogenous troponin (cTn) complexes directly from human heart tissue. Our results not only reveal the native complex assembly, post-translational modification landscape, and Ca2+ binding dynamics of the cTn complex but also enable us to propose a paradigm for structural and dynamical characterization of endogenous native protein complexes from human tissues.

INSTRUMENT(S): timsTOF Pro, maXis, solariX, impact

ORGANISM(S): Human

SUBMITTER: Ying Ge

PROVIDER: MSV000092130 | MassIVE | Thu Jun 08 09:53:00 BST 2023

SECONDARY ACCESSION(S): PXD042825

REPOSITORIES: MassIVE

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