8b46
Crystal structure of the SUN1-KASH6 9:9 complex
Structural highlights
FunctionSUN1_HUMAN As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton (PubMed:18039933, PubMed:18396275). The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning (By similarity). Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration (By similarity). Involved in telomere attachment to nuclear envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC complex in which SUN1 and SUN2 seem to act at least partial redundantly (By similarity). Required for gametogenesis and involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis (By similarity). Helps to define the distribution of nuclear pore complexes (NPCs) (By similarity). Required for efficient localization of SYNE4 in the nuclear envelope (By similarity). May be involved in nuclear remodeling during sperm head formation in spermatogenenis (By similarity). May play a role in DNA repair by suppressing non-homologous end joining repair to facilitate the repair of DNA cross-links (PubMed:24375709).[UniProtKB:Q9D666][1] [2] [3] Publication Abstract from PubMedThe LINC complex transmits cytoskeletal forces into the nucleus to control the structure and movement of nuclear contents. It is formed of nuclear SUN and cytoplasmic KASH proteins, which interact within the nuclear lumen, immediately below the outer nuclear membrane. However, the symmetrical location of KASH molecules within SUN-KASH complexes in previous crystal structures has been difficult to reconcile with the steric requirements for insertion of their immediately upstream transmembrane helices into the outer nuclear membrane. Here, we report the crystal structure of the SUN-KASH complex between SUN1 and JAW1/LRMP (KASH6) in an asymmetric 9:6 configuration. This intertwined assembly involves two distinct KASH conformations such that all six KASH molecules emerge on the same molecular surface. Hence, they are ideally positioned for insertion of upstream sequences into the outer nuclear membrane. Thus, we report a SUN-KASH complex architecture that appears to be directly compatible with its biological role. The crystal structure of SUN1-KASH6 reveals an asymmetric LINC complex architecture compatible with nuclear membrane insertion.,Gurusaran M, Erlandsen BS, Davies OR Commun Biol. 2024 Jan 30;7(1):138. doi: 10.1038/s42003-024-05794-6. PMID:38291267[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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