4FI9

Structure of human SUN-KASH complex

Summary for 4FI9

• Entry DOI: 10.2210/pdb4fi9/pdb
• Descriptor: SUN domain-containing protein 2, Nesprin-2 (3 entities in total)
• Functional Keywords: linc complex, transmembrane protein, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus inner membrane; Single-pass type II membrane protein: Q9UH99; Nucleus outer membrane; Single-pass type IV membrane protein; Cytoplasmic side (Potential): Q8WXH0
• Total number of polymer chains: 2
• Total formula weight: 23580.50

Authors

Wang, W.J.,Shi, Z.B. (deposition date: 2012-06-08, release date: 2012-07-18, Last modification date: 2024-11-20)

Primary citation

Wang, W.,Shi, Z.,Jiao, S.,Chen, C.,Wang, H.,Liu, G.,Wang, Q.,Zhao, Y.,Greene, M.I.,Zhou, Z.
Structural insights into SUN-KASH complexes across the nuclear envelope.
Cell Res., 22:1440-1452, 2012

PubMed Abstract: Linker of the nucleoskeleton and the cytoskeleton (LINC) complexes are composed of SUN and KASH domain-containing proteins and bridge the inner and outer 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 closely resembles the SUN domain in its apo state. A major conformational change involves the AA'-loop of KASH-bound SUN domain, which rearranges to form a mini β-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, 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.

PubMed: 22945352
DOI: 10.1038/cr.2012.126

Experimental method

X-RAY DIFFRACTION (3.05 Å)