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KMID : 0624620170500100485
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BMB Reports
2017 Volume.50 No. 10 p.485 ~ p.486
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Rescuing p53 from mdm2 by a pre-structured motif in intrinsically unfolded SUMO specific protease 4
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Kim Do-Hyoung
Lee Che-Wook
Kim Bom
Lee Si-Hyung
Han Kyou-Hoon
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Abstract
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Many intrinsically unstructured/unfolded proteins (IUPs) contain transient local secondary structures even though they are “unstructured” in a tertiary sense. These local secondary structures are named “pre-structured motifs (PreSMos)” and in fact are the specificity determinants for IUP-target binding, i.e., the active sites in IUPs. Using high-resolution NMR we have delineated a PreSMo active site in the intrinsically unfolded mid-domain (residues 201?300) of SUMO-specific protease 4 (SUSP4). This 29-residue motif which we termed a p53 rescue motif can protect p53 from mdm2 quenching by binding to the p53-helix binding pocket in mdm2(3?109). Our work demonstrates that the PreSMo approach is quite effective in providing a structural rationale for interactions of p53-mdm2-SUSP4 and opens a novel avenue for designing mdm2-inhibiting anticancer compounds.
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KEYWORD
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IUP, Mdm2, p53, PreSMo, SUSP4
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