6xf2
Nesprin-1G (aa2070-2200)-FHOD1(aa1-339) complex, H. sapiens
Structural highlights
DiseaseSYNE1_HUMAN Autosomal recessive myogenic arthrogryposis multiplex congenita;Autosomal dominant Emery-Dreifuss muscular dystrophy;Autosomal recessive ataxia, Beauce type. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionSYNE1_HUMAN Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. May be involved in the maintenance of nuclear organization and structural integrity. Connects nuclei to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm. May be required for centrosome migration to the apical cell surface during early ciliogenesis.[1] [2] Publication Abstract from PubMedThe nuclear position in eukaryotes is controlled by a nucleo-cytoskeletal network, critical in cell differentiation, division, and movement. Forces are transmitted through conserved Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes that traverse the nuclear envelope and engage on either side of the membrane with diverse binding partners. Nesprin-2-giant (Nes2G), a LINC element in the outer nuclear membrane, connects to the actin directly as well as through FHOD1, a formin primarily involved in actin bundling. Here, we report the crystal structure of Nes2G bound to FHOD1 and show that the presumed G-binding domain of FHOD1 is rather a spectrin repeat (SR) binding enhancer for the neighboring FH3 domain. The structure reveals that SR binding by FHOD1 is likely not regulated by the diaphanous-autoregulatory domain helix of FHOD1. Finally, we establish that Nes1G also has one FHOD1 binding SR, indicating that these abundant, giant Nesprins have overlapping functions in actin-bundle recruitment for nuclear movement. Structures of FHOD1-Nesprin1/2 complexes reveal alternate binding modes for the FH3 domain of formins.,Lim SM, Cruz VE, Antoku S, Gundersen GG, Schwartz TU Structure. 2021 Jun 3;29(6):540-552.e5. doi: 10.1016/j.str.2020.12.013. Epub 2021 , Jan 19. PMID:33472039[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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