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PRODID:-//Iowa State University CALS LAS Web Team//sites.iastate.edu//EN
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UID:20240412T202000-940-www.chem.iastate.edu
DTSTART:20240412T202000Z
SEQUENCE:0
TRANSP:OPAQUE
DTEND:20240412T212000Z
LOCATION:1352 Gilman
SUMMARY:George Lisi - \"Allosteric and Redox-dependent Regulation of MIF th
 rough Molecular Space and Time\"
CLASS:PUBLIC
DESCRIPTION:Professor George Lisi\, Brown University\, BioPhysicalMacrophag
 e migration inhibitory factor (MIF) is a multifunctional immunoregulatory 
 protein that is a key player in the innate immune response. Despite its sy
 mmetric trimer structure composed of small\, identical protein subunits\, 
 MIF contains three enzymatic active sites\, a pro-inflammatory receptor bi
 nding site\, and is implicated in more than 30 protein-protein interaction
 s and diseases. &nbsp\;MIF is implicated in nearly all inflammatory diseas
 es and several cancers\, though the mechanism by which MIF engages in prom
 iscuous interactions with substrates and partner proteins is unclear at th
 e biophysical level\, hampering the visualization and targeting of MIF dis
 ease states. This talk will describe the structural and dynamic factors th
 at facilitate multi-domain crosstalk and control multiple biological activ
 ities in MIF and its homologs. Primarily using solution NMR\, the highly d
 ynamic MIF structure will be connected to rearrangements that tune its spe
 cific catalytic and pro-inflammatory functions.A secondary focus will be o
 n efforts to leverage biochemical stimuli such as redox conditions and mut
 ations to understand altered MIF structures and signatures of its “disea
 se states.” NMR spectroscopy will reveal real-time\, redox-dependent alt
 erations to the MIF solution structure\, and through mass spectrometry\, d
 etect residue-level modifications that acts as “molecular switches” fo
 r selective binding. Biophysical studies implicate redox-dependent structu
 ral dynamics as a means to toggle the MIF functions\, and these motions ar
 e leveraged in the discovery of latent allosteric sites through mutational
  analysis. A disruption of redox-dependent structural triggers within MIF 
 attenuate its pro-inflammatory CD74 receptor activation in vivo\, suggesti
 ng sites of redox sensitivity can be targets for structure-based drug desi
 gn aimed at modulating MIF its pathological function.\n\nMore information 
 at: https://www.chem.iastate.edu/event/2024/george-lisi-allosteric-and-red
 ox-dependent-regulation-mif-through-molecular-space-and
DTSTAMP:20261016T121518Z
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