Structural highlights
Function
[HRS_DROME] Essential role in endosome membrane invagination and formation of multivesicular bodies, MVBs. Required during gastrulation and appears to regulate early embryonic signaling pathways. Inhibits tyrosine kinase receptor signaling by promoting degradation of the tyrosine-phosphorylated, active receptor, potentially by sorting activated receptors into MVBs. The MVBs are then trafficked to the lysosome where their contents are degraded.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We have determined the 2 A X-ray structure of the 219-residue N-terminal VHS and FYVE tandem domain unit of Drosophila Hrs. The unit assumes a pyramidal structure in which the much larger VHS domain (residues 1-153) forms a rectangular base and the FYVE domain occupies the apical end. The VHS domain is comprised of an unusual "superhelix" of eight alpha helices, and the FYVE domain is mainly built of loops, two double-stranded antiparallel sheets, and a helix stabilized by two tetrahedrally coordinated zinc atoms. The two-domain structure forms an exact 2-fold-related homodimer through antiparallel association of mainly FYVE domains. Dimerization creates two identical pockets designed for binding ligands with multiple negative charges such as citrate or phosphatidylinositol 3-phosphate.
Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction.,Mao Y, Nickitenko A, Duan X, Lloyd TE, Wu MN, Bellen H, Quiocho FA Cell. 2000 Feb 18;100(4):447-56. PMID:10693761[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lloyd TE, Atkinson R, Wu MN, Zhou Y, Pennetta G, Bellen HJ. Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell. 2002 Jan 25;108(2):261-9. PMID:11832215
- ↑ Mao Y, Nickitenko A, Duan X, Lloyd TE, Wu MN, Bellen H, Quiocho FA. Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction. Cell. 2000 Feb 18;100(4):447-56. PMID:10693761
