Wellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh, EH9 3BF, UK.
Commun Biol. 2024 Jan 30;7(1):138. doi: 10.1038/s42003-024-05794-6.
The 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.
LINC 复合物将细胞骨架力传递到细胞核内，以控制核内物质的结构和运动。它由核 SUN 和质膜 KASH 蛋白组成，这些蛋白在核腔内在核外膜的下方相互作用。然而，在以前的晶体结构中，KASH 分子在 SUN-KASH 复合物中的对称位置与它们上游跨膜螺旋插入核外膜的空间位阻要求很难协调。在这里，我们报告了 SUN1 和 JAW1/LRMP（KASH6）之间以非对称 9:6 构象形成的 SUN-KASH 复合物的晶体结构。这种交织的组装涉及两种不同的 KASH 构象，使得所有六个 KASH 分子都出现在同一分子表面上。因此，它们非常适合将上游序列插入核外膜。因此，我们报告了一种 SUN-KASH 复合物结构，它似乎与其生物学功能直接兼容。
