Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction.
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.
Mao
Y
Y
Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA.
Nickitenko
A
A
Duan
X
X
Lloyd
T E
TE
Wu
M N
MN
Bellen
H
H
Quiocho
F A
FA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D004330:Drosophila; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D016335:Zinc Fingers
D056827:Endosomal Sorting Complexes Required for Transport; D008024:Ligands; D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; C055525:phosphatidylinositol 3-phosphate