2ns2

From Proteopedia

Revision as of 15:50, 20 March 2008

Crystal Structure of Spindlin1

Overview

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 beta-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.

Disease

Known diseases associated with this structure: Dent syndrome OMIM:[300535], Fibrocalculous pancreatic diabetes, susceptibility to OMIM:[167790], Lowe syndrome OMIM:[300535], Pancreatitis, hereditary OMIM:[167790], Tropical calcific pancreatitis OMIM:[167790]

About this Structure

2NS2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of human spindlin1. Tandem tudor-like domains for cell cycle regulation., Zhao Q, Qin L, Jiang F, Wu B, Yue W, Xu F, Rong Z, Yuan H, Xie X, Gao Y, Bai C, Bartlam M, Pei X, Rao Z, J Biol Chem. 2007 Jan 5;282(1):647-56. Epub 2006 Nov 1. PMID:17082182

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