title: Structure of Sad1-UNC84 homology (SUN) domain defines features of molecular bridge in nuclear envelope.
abstract: The SUN (Sad1-UNC-84 homology) domain is conserved in a number of nuclear envelope proteins involved in nuclear migration, meiotic telomere tethering, and antiviral responses. The LINC (linker of nucleoskeleton and cytoskeleton) complex, formed by the SUN and the nesprin proteins at the nuclear envelope, serves as a mechanical linkage across the nuclear envelope. Here we report the crystal structure of the SUN2 protein SUN domain, which reveals a homotrimer. The SUN domain is sufficient to mediate binding to the KASH (Klarsicht, ANC-1, and Syne homology) domain of nesprin 2, and the regions involved in the interaction have been identified. Binding of the SUN domain to the KASH domain is abolished by deletion of a region important for trimerization or by point mutations associated with nuclear migration failure. We propose a model of the LINC complex, where the SUN and the KASH domains form a higher ordered oligomeric network in the nuclear envelope. These findings provide the structural basis for understanding the function and the regulation of the LINC complex.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Zhaocai
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiulian
authors.initials: X
authors.lastname: Du
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cai
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Song
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.forename: Takako
authors.initials: T
authors.lastname: Mizuno
authors.forename: Emi
authors.initials: E
authors.lastname: Suzuki
authors.forename: Marla Rosanne
authors.initials: MR
authors.lastname: Yee
authors.forename: Alan
authors.initials: A
authors.lastname: Berezov
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Murali
authors.forename: Shiaw-Lin
authors.initials: SL
authors.lastname: Wu
authors.forename: Barry L
authors.initials: BL
authors.lastname: Karger
authors.forename: Mark I
authors.initials: MI
authors.lastname: Greene
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D003599:Cytoskeleton / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009685:Nuclear Envelope / Q000737:chemistry* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C413025:SUN2 protein, human; C485904:SYNE2 protein, human