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@ARTICLE{Chan:637345,
      author       = {Chan, Hsin-Ju and Krichel, Boris and Bandura, Liam J. and
                      Chapman, Emily A. and Rogers, Holden T. and Fischer, Matthew
                      S. and Roberts, David S. and Gao, Zhan and Wang, Man-Di and
                      Wu, Jingshing and Uetrecht, Charlotte and Jin, Song and Ge,
                      Ying},
      title        = {{S}tructural {H}eterogeneity of {P}roteoform-{L}igand
                      {C}omplexes in {A}denosine {M}onophosphate-{A}ctivated
                      {P}rotein {K}inase {U}ncovered by {I}ntegrated {T}op-{D}own
                      {M}ass {S}pectrometry},
      journal      = {Journal of the American Chemical Society},
      volume       = {147},
      number       = {34},
      issn         = {0002-7863},
      address      = {Washington, DC},
      publisher    = {ACS Publications},
      reportid     = {PUBDB-2025-03837},
      pages        = {30809 - 30819},
      year         = {2025},
      note         = {Waiting for fulltext},
      abstract     = {Adenosine monophosphate-activated protein kinase (AMPK) is
                      a heterotrimeric complex (αβγ) that serves as a master
                      regulator of cellular metabolism, making it a prominent drug
                      target for various diseases. Post-translational
                      modifications (PTMs) and ligand binding significantly affect
                      the activity and function of AMPK. However, the dynamic
                      interplay of PTMs, noncovalent interactions, and
                      higher-order structures of the kinase complex remains poorly
                      understood. Herein, we report for the first time the
                      structural heterogeneity of the AMPK complex arising from
                      ligand binding and proteoforms─protein products derived
                      from PTMs, alternative splicing, and genetic
                      variants─using integrated native and denatured top-down
                      mass spectrometry (TDMS). The fully intact AMPK
                      heterotrimeric complex exhibits heterogeneity due to
                      phosphorylation and multiple adenosine monophosphate (AMP)
                      binding states. Native TDMS delineates the subunit
                      composition, AMP binding stoichiometry, and higher-order
                      structure of AMPK complex, while denatured TDMS
                      comprehensively characterizes the proteoforms and localizes
                      the phosphorylation site. Notably, by integrating native
                      TDMS and AlphaFold, we elucidate a flexibly connected
                      regulatory region of AMPK β subunit that was previously
                      unresolvable with traditional structural biology tools. Our
                      findings offer new perspectives on protein kinase regulation
                      and establish a versatile framework for comprehensive
                      characterization of proteoform-ligand complexes.},
      cin          = {CSSB-LIV/DESY-CU},
      ddc          = {540},
      cid          = {$I:(DE-H253)CSSB-LIV_DESY-CU-20220525$},
      pnm          = {633 - Life Sciences – Building Blocks of Life: Structure
                      and Function (POF4-633) / Top-AMPK - Putting the top down on
                      AMPK protein complex (101068151) / SPOCkS MS - Sampling
                      Protein cOmplex Conformational Space with native top down
                      Mass Spectrometry (759661)},
      pid          = {G:(DE-HGF)POF4-633 / G:(EU-Grant)101068151 /
                      G:(EU-Grant)759661},
      experiment   = {EXP:(DE-MLZ)NOSPEC-20140101},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1021/jacs.5c06950},
      url          = {https://bib-pubdb1.desy.de/record/637345},
}