Mao Y, Nickitenko A, Duan X, Lloyd T E, Wu M N, Bellen H, Quiocho F A
Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA.
Cell. 2000 Feb 18;100(4):447-56. doi: 10.1016/s0092-8674(00)80680-7.
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.
我们已经确定了果蝇Hrs的219个残基的N端VHS和FYVE串联结构域单元的二维X射线结构。该单元呈金字塔结构，其中大得多的VHS结构域（1 - 153位残基）形成矩形底部，而FYVE结构域占据顶端。VHS结构域由八个α螺旋组成的不寻常“超螺旋”构成，FYVE结构域主要由环、两个双链反平行片层以及由两个四面体配位锌原子稳定的一个螺旋组成。这两个结构域通过主要是FYVE结构域的反平行缔合形成一个精确的二倍体相关同源二聚体。二聚化产生两个相同的口袋，用于结合具有多个负电荷的配体，如柠檬酸盐或磷脂酰肌醇3 - 磷酸。
