Coiled-Coil Domains of SUN Proteins as Intrinsic Dynamic Regulators

• Published in: Structure (London) Vol. 24; no. 1; pp. 80 - 91
• Main Authors: Nie, Si, Ke, Huimin, Gao, Feng, Ren, Jinqi, Wang, Mingzhu, Huo, Lin, Gong, Weimin, Feng, Wei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 05.01.2016
• Subjects: Amino Acid Sequence; Animals; coiled-coil; LINC complex; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Mice; Molecular Dynamics Simulation; Molecular Sequence Data; nuclear envelope; Protein Binding; Protein Multimerization; Protein Structure, Tertiary; SUN protein; Telomere-Binding Proteins - chemistry; Telomere-Binding Proteins - metabolism; LINC complex; nuclear envelope; coiled-coil; SUN protein
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2015.10.024

SUN proteins are the core components of LINC complexes that span across the nuclear envelope for nuclear positioning and migration. SUN proteins contain at least one predicted coiled-coil domain preceding the SUN domain. Here, we found that the two coiled-coil domains (CC1 and CC2) of SUN2 exhibit distinct oligomeric states. CC2 is a monomer in solution. The structure of the CC2-SUN monomer revealed that CC2 unexpectedly folds as a three-helix bundle that interacts with the SUN domain and locks it in an inactive conformation. In contrast, CC1 is a trimer. The structure of the CC1 trimer demonstrated that CC1 is an imperfect coiled coil for the trimerization and activation of the SUN domain. Modulations of CC1 and CC2 dictate different oligomeric states of CC1-CC2-SUN, which is essential for LINC complex formation. Thus, the two coiled-coil domains of SUN2 act as the intrinsic dynamic regulators for controlling the SUN domain activity. [Display omitted] •The two coiled-coil domains of SUN2 exhibit distinct oligomeric states•CC2 forms a three-helix bundle to lock the SUN domain in an inactive conformation•CC1 is a trimeric coiled coil for the trimerization and activation of the SUN domain•The two coiled-coil domains of SUN2 act as the intrinsic dynamic regulators SUN proteins contain at least one predicted coiled-coil domain preceding the SUN domain. Nie et al. determine the crystal structures of the different fragments including the coiled-coil and SUN domains from SUN2, which provide the molecular mechanism underlying the internal coiled-coil-mediated regulation of SUN proteins.