Structural and Functional Studies of the 252 kDa Nucleoporin ELYS Reveal Distinct Roles for Its Three Tethered Domains

• Published in: Structure (London) 2013-04, Vol.21 (4), p.572-580
• Main Authors: Bilokapic, Silvija, Schwartz, Thomas U.
• Format: Article
• Language: English
• Subjects: Anchorages; Assembly; Breaking down; Cell division; Cell Line; Chromatin - metabolism; Crystal structure; Crystallization; DNA-Binding Proteins - chemistry; Humans; Models, Molecular; Nuclear Pore - metabolism; Nuclear Pore Complex Proteins - chemistry; Porosity; Protein Conformation; Protein Interaction Domains and Motifs; Scaffolding; Tethering; Transcription Factors - chemistry; X-Ray Diffraction
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2013.02.006

In metazoa, the nuclear envelope (NE), together with the embedded nuclear pore complexes (NPCs), breaks down and reassembles during cell division. It is suggested that ELYS, a nucleoporin, binds to chromatin in an initial step of postmitotic NPC assembly and subsequently recruits the essential Y-subcomplex, the major scaffolding unit of the NPC. Here, we show that ELYS contains three domains: an N-terminal β-propeller domain, a central α-helical domain, and a C-terminal disordered region. While the disordered region is responsible for the interactions with chromatin, the two preceding domains synergistically mediate tethering to the NPC. We present the crystal structure of the seven-bladed β-propeller domain at 1.9 Å resolution. Analysis of the β-propeller surface reveals the regions that are required for NPC anchorage. We discuss the possible roles of ELYS in the context of the NPC scaffold architecture. ► The vertebrate nucleoporin ELYS contains three structurally distinct domains ► β-propeller and α-helical domain synergistically mediate integration into the NPC ► Crystal structure of the N-terminal domain from M. musculus at 1.9 Å is presented ► In vivo data using structure-based mutants reveal the determinants of NPC integration Nuclear pore complexes (NPCs) are very large protein assemblies, and their structural analysis resembles solving a complicated jigsaw puzzle. Bilokapic and Schwartz add a piece to the puzzle by solving a partial structure of nucleoporin ELYS. These data refine the emerging picture of a highly modular NPC assembly.