Heterotrifunctional chemical cross-linking mass spectrometry confirms physical interaction between human frataxin and ISU.
The progressive neurodegenerative disease Friedreich's ataxia is caused by a decreased level of expression of frataxin, a putative iron chaperone. Frataxin is thought to transiently interact with ISU, the scaffold protein onto which iron-sulfur clusters are assembled, to deliver ferrous iron. Photoreactive heterotrifunctional chemical cross-linking confirmed the interaction between frataxin and ISU in the presence of iron and validated that transient interactions can be covalently trapped with this method. Because frataxin may participate in transient interactions with other mitochondrial proteins, this cross-linking approach may reveal new protein partners and pathways in which it interacts and help deduce direct, downstream consequences of its deficiency.
Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487, USA.
Heather M
HM
Watson
Leslie E
LE
Gentry
Awuri P
AP
Asuru
Yu
Y
Wang
Stevan
S
Marcus
Laura S
LS
Busenlehner
D000595:Amino Acid Sequence; D005621:Friedreich Ataxia / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055668:Photochemical Processes; D025941:Protein Interaction Mapping; D016415:Sequence Alignment; D014466:Ultraviolet Rays; D000096923:Frataxin
D007501:Iron; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D000096923:Frataxin; C506160:ISCU protein, human