Chaperonin TRiC/CCT Recognizes Fusion Oncoprotein AML1-ETO through Subunit-Specific Interactions.
AML1-ETO is the translational product of a chimeric gene created by the stable chromosome translocation t (8;21)(q22;q22). It causes acute myeloid leukemia (AML) by dysregulating the expression of genes critical for myeloid cell development and differentiation and recently has been reported to bind multiple subunits of the mammalian cytosolic chaperonin TRiC (or CCT), primarily through its DNA binding domain (AML1-175). Through these interactions, TRiC plays an important role in the synthesis, folding, and activity of AML1-ETO. Using single-particle cryo-electron microscopy, we demonstrate here that a folding intermediate of AML1-ETO's DNA-binding domain (AML1-175) forms a stable complex with apo-TRiC. Our structure reveals that AML1-175 associates directly with a specific subset of TRiC subunits in the open conformation.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas.
Soung-Hun
SH
Roh
Division of Internal Medicine, Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas.
Moses M
MM
Kasembeli
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas.
Jesús G
JG
Galaz-Montoya
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas. Electronic address: wah@bcm.edu.
Wah
W
Chiu
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas; Division of Internal Medicine, Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: djtweardy@mdanderson.org.
David J
DJ
Tweardy
D015153:Blotting, Western; D056404:Chaperonin Containing TCP-1 / Q000378:metabolism*; D002850:Chromatography, Gel; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D004247:DNA / Q000378:metabolism; D017612:Gold Compounds; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D021621:Imaging, Three-Dimensional; D013058:Mass Spectrometry; D053768:Metal Nanoparticles; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D000072417:Protein Domains; D017510:Protein Folding; D055503:Protein Multimerization; D055550:Protein Stability; D000075142:RUNX1 Translocation Partner 1 Protein
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D017612:Gold Compounds; D018840:HSP70 Heat-Shock Proteins; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D004247:DNA; D056404:Chaperonin Containing TCP-1