Structure of human spindlin1. Tandem tudor-like domains for cell cycle regulation

Abstract 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 disturb the cell cycle. Here we report the crystal structure of human spindlin1 to 2.2A of resolution, representing the first three-dimensional structure from the spin/ssty (Y-linked spermiogenesis-specific transcript) gene family. The refined structure, containing three repeats of five/four anti-parallel β-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 spindlin1. 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 regulation and other functions.