Structure of Human Spindlin1

Spindlin1, a meiotic spindle-binding protein that is highly expressed in ovarian cancer cells, was first identified as a gene involved in gametogenesis. It appeared to be a target for cell cycle-dependent phosphorylation and was demonstrated to dis- turb the cell cycle. Here we report the crystal structure of human spindlin1 to 2.2 Aof resolution, representing the first three- dimensional structure from the spin/ssty (Y-linked spermiogen- esis-specific transcript) gene family. The refined structure, con- taining three repeats of five/four anti-parallel -strands, exhibits a novel arrangement of tandem Tudor-like domains. Two phosphate ions, chelated by Thr-95 and other residues, appear to stabilize the long loop between domains I and II, which might mediate the cell cycle regulation activity of spin- dlin1. Flow cytometry experiments indicate that cells expressing spindlin1 display a different cell cycle distribution in mitosis, whereas those expressing a T95A mutant, which had a great decrease in phosphorous content, have little effect on the cell cycle. We further identified associations of spindlin1 with nucleic acid to provide a biochemical basis for its cell cycle reg- ulation and other functions.