What is it about?
The NHL domain is an important protein motif functioning as an interactor with many macromolecules for diverse signaling pathways. This domain presents also in human E3 ligase TRIMs, called TRIM-NHL, but little is known about their structures and functions. We present a comprehensive set of the crystal structures of the NHL domains of three of the four human TRIM E3 ligases revealing evolutionary divergence that differentiates intrinsic properties and potentially recognition functions of this conserved protein domain, diversifying the biological functions of TRIM–NHL proteins.
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Why is it important?
Little remains unknown regarding structures and functions of many E3 ligases which are an important protein involving in ubiquitin signaling. We studied a subfamily of E3 ligase TRIM-NHL by providing for the first time the crystal structures of the NHL motif of three of four members. Family-wide analyses highlight similarity as well as differences that potentially differentiate their functions. These structural model show also that the NHL domains of these TRIM E3 ligases are the hot spot for disease-linked mutations.
Perspectives
The molecular insights highlights evolutionary divergence that differentiates intrinsic properties and potentially recognition functions of this conserved NHL protein domain. In addition, these structures may serve as a template for further study to identify the interaction partners as well as the functions of these TRIM NHLs and potentially the development of small molecule binders that might find applications in the development of PROTACs and molecular glues.
apirat chaikuad
Read the Original
This page is a summary of: Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family, IUCrJ, September 2022, International Union of Crystallography,
DOI: 10.1107/s2052252522008582.
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