Structural highlights
Function
SUN1_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 PubMed
The LINC complex, consisting of interacting SUN and KASH proteins, mechanically couples nuclear contents to the cytoskeleton. In meiosis, the LINC complex transmits microtubule-generated forces to chromosome ends, driving the rapid chromosome movements that are necessary for synapsis and crossing over. In somatic cells, it defines nuclear shape and positioning, and has a number of specialised roles, including hearing. Here, we report the X-ray crystal structure of a coiled-coiled domain of SUN1's luminal region, providing an architectural foundation for how SUN1 traverses the nuclear lumen, from the inner nuclear membrane to its interaction with KASH proteins at the outer nuclear membrane. In combination with light and X-ray scattering, molecular dynamics and structure-directed modelling, we present a model of SUN1's entire luminal region. This model highlights inherent flexibility between structured domains, and raises the possibility that domain-swap interactions may establish a LINC complex network for the coordinated transmission of cytoskeletal forces.
Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1.,Gurusaran M, Biemans JJ, Wood CW, Davies OR Front Cell Dev Biol. 2023 Jun 21;11:1144277. doi: 10.3389/fcell.2023.1144277. , eCollection 2023. PMID:37416798[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bupp JM, Martin AE, Stensrud ES, Jaspersen SL. Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3. J Cell Biol. 2007 Dec 3;179(5):845-54. Epub 2007 Nov 26. PMID:18039933 doi:https://dx.doi.org/10.1083/jcb.200706040
- ↑ Stewart-Hutchinson PJ, Hale CM, Wirtz D, Hodzic D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp Cell Res. 2008 May 1;314(8):1892-905. doi: 10.1016/j.yexcr.2008.02.022. Epub , 2008 Mar 12. PMID:18396275 doi:https://dx.doi.org/10.1016/j.yexcr.2008.02.022
- ↑ Li P, Meinke P, Huong le TT, Wehnert M, Noegel AA. Contribution of SUN1 mutations to the pathomechanism in muscular dystrophies. Hum Mutat. 2014 Apr;35(4):452-61. doi: 10.1002/humu.22504. Epub 2014 Jan 13. PMID:24375709 doi:https://dx.doi.org/10.1002/humu.22504
- ↑ Gurusaran M, Biemans JJ, Wood CW, Davies OR. Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1. Front Cell Dev Biol. 2023 Jun 21;11:1144277. PMID:37416798 doi:10.3389/fcell.2023.1144277