期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：41
页码：16498-16503
DOI：10.1073/pnas.1214557109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The coatomer module of the nuclear pore complex borders the cylinder-like nuclear pore-membrane domain of the nuclear envelope. In evolution, a single coatomer module increases in size from hetero-heptamer (Saccharomyces cerevisiae) to hetero-octamer (Schizosaccharomyces pombe) to hetero-nonamer (Metazoa). Notably, the heptamer-octamer transition proceeds through the acquisition of the nucleoporin Nup37. How Nup37 contacts the heptamer remained unknown. Using recombinant nucleoporins, we show that Sp-Nup37 specifically binds the Sp-Nup120 member of the hetero-heptamer but does not bind an Sc-Nup120 homolog. To elucidate the Nup37-Nup120 interaction at the atomic level, we carried out crystallographic analyses of Sp-Nup37 alone and in a complex with an N-terminal, [~]110-kDa fragment of Sp-Nup120 comprising residues 1-950. Corroborating structural predictions, we determined that Nup37 folds into a seven-bladed {beta}-propeller. Several disordered surface regions of the Nup37 {beta}-propeller assume structure when bound to Sp-Nup120. The N-terminal domain of Sp-Nup1201-950 also folds into a seven-bladed propeller with a markedly protruding 6D-7A insert and is followed by a contorted helical domain. Conspicuously, this 6D-7A insert contains an extension of 50 residues which also is highly conserved in Metazoa but is absent in Sc-Nup120. Strikingly, numerous contacts with the Nup37 {beta}-propeller are located on this extension of the 6D-7A insert. Another contact region is situated toward the end of the helical region of Sp-Nup1201-950. Our findings provide information about the evolution and the assembly of the coatomer module of the nuclear pore complex.
