Nat CommunJClub
HERC2-UBE3A structure uncovers a domain-motif protein network potentially altered in Angelman and related syndromes.
Nature Communications · · Journal Article · Open access
Demenge, Lim + more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
The HERC2-UBE3A complex interface is defined by HERC2’s RLD2 domain binding a UBE3A “DxDKDxD” motif, revealing a conserved protein-network architecture.
- Why it matters: Altered HERC2 and UBE3A dosage in Dup15q Syndrome and Angelman Syndrome is linked to intellectual disability, but the molecular interaction logic and downstream partners were unclear.
- What they did: The authors used quantitative binding assays, X-ray crystallography, and sequence conservation analysis to map the core interface and identify additional HERC2-binding “DxDKDxD” motifs in brain-development proteins, then tested HERC2–DOCK10 in hippocampal neurons.
- The result: HERC2 knockdown via siRNA affects DOCK10 GEF activity, and mutating the HERC2-binding motif in DOCK10 disrupts both GEF activity and dendritic spine formation, implying dosage-linked shifts in RLD2-mediated complexes.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.
- Open access