4gq1

Publication Abstract from PubMed

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, approximately 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-Nup120(1-950) 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-Nup120(1-950). Our findings provide information about the evolution and the assembly of the coatomer module of the nuclear pore complex.

Structural evolution of the membrane-coating module of the nuclear pore complex.,Liu X, Mitchell JM, Wozniak RW, Blobel G, Fan J Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16498-503. doi:, 10.1073/pnas.1214557109. Epub 2012 Sep 26. PMID:23019579^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.