Structure and nucleic acid binding activity of the nucleoporin Nup157.
At the center of the nuclear pore complex (NPC) is a uniquely versatile central transport channel. Structural analyses of distinct segments ("protomers") of the three "channel" nucleoporins yielded a model for how this channel is constructed. Its principal feature is a midplane ring that can undergo regulated diameter changes of as much as an estimated 30 nm. To better understand how a family of "adaptor" nucleoporins--concentrically surrounding this channel--might cushion these huge structural changes, we determined the crystal structure of one adaptor nucleoporin, Nup157. Here, we show that a recombinant Saccharomyces cerevisiae Nup157 protomer, representing two-thirds of Nup157 (residues 70-893), folds into a seven-bladed β-propeller followed by an α-helical domain, which together form a C-shaped architecture. Notably, the structure contains a large patch of positively charged residues, most of which are evolutionarily conserved. Consistent with this surface feature, we found that Nup157(70-893) binds to nucleic acids, although in a sequence-independent manner. Nevertheless, this interaction supports a previously reported role of Nup157, and its paralogue Nup170, in chromatin organization. Based on its nucleic acid binding capacity, we propose a dual location and function of Nup157. Finally, modeling the remaining C-terminal portion of Nup157 shows that it projects as a superhelical stack from the compact C-shaped portion of the molecule. The predicted four hinge regions indicate an intrinsic flexibility of Nup157, which could contribute to structural plasticity within the NPC.
Laboratory of Cell Biology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
Hyuk-Soo
HS
Seo
Bartlomiej J
BJ
Blus
Nina Z
NZ
Jankovic
Günter
G
Blobel
D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D003460:Crystallization; D004926:Escherichia coli; D008958:Models, Molecular; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000378:metabolism*; D009696:Nucleic Acids / Q000378:metabolism*; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D013499:Surface Properties; D014961:X-Ray Diffraction
C097179:NUP157 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009696:Nucleic Acids; D029701:Saccharomyces cerevisiae Proteins
DNA-binding protein; RNA-binding protein; X-ray crystallography; gene gating