LINC complexes are composed of SUN and KASH domain-containing proteins and bridge the inner and outer double membranes of the nuclear envelope.LINC complexes play critical roles in nuclear positioning,cell polarization and cellular stiffness. Previously, we reported the homotrimeric structure of human SUN2. We have now determined the crystal structure of the human SUN2-KASH complex.In the complex structure,the SUN domain homotrimer binds to three independent "hook"like KASH peptides.The overall conformation of the SUN domain in the complex structure closely resembles the SUN domain in its apo state.In a major conformational change,the AA-Ioop rearranges to form a mini beta-sheet that interacts with the KASH peptide.The PPPT motif of the KASH domain fits tightly into a hydrophobic pocket on the homotrimeric interface of the SUN domain,which we termed the BI pocket.Moreover,two adjacent protomers of the SUN domain homotrimer sandwich the KASH domain by hydrophobic interaction and hydrogen bonding.Mutations of these binding sites disrupt or reduce the association between the SUN and KASH domains in vitro.In addition,the transfection of wild-type,but not mutant,SUN2 promotes cell migration in Ovcar-3 cells.These results provide a structural model of the LINC complex,which is essential for additional study of the physical and functional coupling between the cytoplasm and the nucleoplasm.