A critical examination of the recently reported crystal structures of the human SMN protein. (29th August 2016)

• Record Type: Journal Article
• Authors: Weiss, Manfred S.; Diederichs, Kay; Read, Randy J.; Panjikar, Santosh; Van Duyne, Gregory D.; Matera, A. Gregory; Fischer, Utz; Grimm, Clemens
• Is Part Of: Human molecular genetics. Volume 25:Number 21(2016:Nov. 01)
• Page Start: 4717
• Page End: 4725
• Publication Date: 2016-08-29
• Subjects: Human molecular genetics -- Periodicals; Human chromosome abnormalities -- Periodicals; 572.8
• DOI: 10.1093/hmg/ddw298
• Languages: English
• ISSNs: 0964-6906

Abstract

Abstract: A recent publication by Seng et al. in this journal reports the crystallographic structure of refolded, full-length SMN protein and two disease-relevant derivatives thereof. Here, we would like to suggest that at least two of the structures reported in that study are incorrect. We present evidence that one of the associated crystallographic datasets is derived from a crystal of the bacterial Sm-like protein Hfq and that a second dataset is derived from a crystal of the bacterial Gab protein. Both proteins are frequent contaminants of bacterially overexpressed proteins which might have been co-purified during metal affinity chromatography. A third structure presented in the Seng et al. paper cannot be examined further because neither the atomic coordinates, nor the diffraction intensities were made publicly available. The Tudor domain protein SMN has been shown to be a component of the SMN complex, which mediates the assembly of RNA-protein complexes of uridine-rich small nuclear ribonucleoproteins (UsnRNPs). Importantly, this activity is reduced in SMA patients, raising the possibility that the aetiology of SMA is linked to RNA metabolism. Structural studies on diverse components of the SMN complex, including fragments of SMN itself have contributed greatly to our understanding of the cellular UsnRNP assembly machinery. Yet full-length SMN has so far evaded structural elucidation. The Seng et al. study claimed to have closed this gap, but based on the results presented here, the only conclusion that can be drawn is that the Seng et al. study is largely invalid and should be retracted from the literature.