Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT Domain
作者： Abiodun A Ogunjimi , Douglas J Briant , Nadia Pece-Barbara , Christine Le Roy , Gianni M Di Guglielmo
DOI: 10.1016/J.MOLCEL.2005.06.028
关键词: Mutagenesis 、 HECT domain 、 Receptor complex 、 Enzyme 、 Ubiquitin ligase activity 、 Ubiquitin 、 Biology 、 Biochemistry 、 Domain (software engineering) 、 Ubiquitin ligase
摘要: The conjugation of ubiquitin to proteins involves a cascade activating (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that commonly signal protein destruction. In TGFβ signaling the inhibitory Smad7 recruits Smurf2, an E3 C2-WW-HECT domain class, receptor complex facilitate degradation. Here, we demonstrate amino-terminal (NTD) stimulates Smurf activity by recruiting E2, UbcH7, HECT domain. A 2.1 resolution X-ray crystal structure Smurf2 reveals it has suboptimal E2 binding pocket could be optimized mutagenesis generate functions independently potently inhibits signaling. Thus, enzyme recognition is not constitutively competent provides point control for regulating ligase through action auxiliary proteins.
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