LINC Complexes Form by Binding of Three KASH Peptides to Domain Interfaces of Trimeric SUN Proteins
نویسندگان
چکیده
Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the nuclear envelope and are composed of KASH and SUN proteins residing in the outer and inner nuclear membrane, respectively. LINC formation relies on direct binding of KASH and SUN in the perinuclear space. Thereby, molecular tethers are formed that can transmit forces for chromosome movements, nuclear migration, and anchorage. We present crystal structures of the human SUN2-KASH1/2 complex, the core of the LINC complex. The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. The peptides bind in three deep and expansive grooves formed between adjacent SUN domains, effectively acting as molecular glue. In addition, a disulfide between conserved cysteines on SUN and KASH covalently links both proteins. The structure provides the basis of LINC complex formation and suggests a model for how LINC complexes might arrange into higher-order clusters to enhance force-coupling.
منابع مشابه
LINCing complex functions at the nuclear envelope
Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the double membrane of the nuclear envelope (NE) and physically connect nuclear structures to cytoskeletal elements. LINC complexes are envisioned as force transducers in the NE, which facilitate processes like nuclear anchorage and migration, or chromosome movements. The complexes are built from members of two evolutionary conserv...
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Correspondence to Gregg G. Gundersen: [email protected] Abbreviations used in this paper: ABD, actin-binding domain; CH, calponin homology; KASH, Klarsicht, ANC-1, and Syne homology; LINC, linker of nucleoskeleton and cytoskeleton; SR, spectrin repeat; SUN, Sad1 and UNC-84; TAN, transmembrane actin–associated nuclear. Introduction The linker of nucleoskeleton and cytoskeleton (LINC) complex is ...
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عنوان ژورنال:
- Cell
دوره 149 شماره
صفحات -
تاریخ انتشار 2012