A critical examination of the recently reported crystal structures of the human SMN protein

Manfred S. Weiss, Kay Diederichs, Randy J. Read, Santosh Panjikar, Gregory D. Van Duyne, A. Gregory Matera, Utz Fischer, Clemens Grimm

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

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 froma crystal of the bacterial Sm-like protein Hfq and that a second dataset is derived froma crystal of the bacterial Gab protein. Both proteins are frequent contaminants of bacterially overexpressed proteins whichmight have been co-purified duringmetal 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 weremade publicly available. The Tudor domain protein SMN has been shown to be a component of the SMN complex, whichmediates 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 RNAmetabolism. Structural studies on diverse components of the SMN complex, including fragments of SMN itself have contributed greatly to our understanding of the cellular UsnRNP assemblymachinery. 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 fromthe literature.

Original languageEnglish
Pages (from-to)4717-4725
Number of pages9
JournalHuman Molecular Genetics
Volume25
Issue number21
DOIs
Publication statusPublished - Nov 2016
Externally publishedYes

Cite this

Weiss, M. S., Diederichs, K., Read, R. J., Panjikar, S., Van Duyne, G. D., Matera, A. G., ... Grimm, C. (2016). A critical examination of the recently reported crystal structures of the human SMN protein. Human Molecular Genetics, 25(21), 4717-4725. https://doi.org/10.1093/hmg/ddw298
Weiss, Manfred S. ; Diederichs, Kay ; Read, Randy J. ; Panjikar, Santosh ; Van Duyne, Gregory D. ; Matera, A. Gregory ; Fischer, Utz ; Grimm, Clemens. / A critical examination of the recently reported crystal structures of the human SMN protein. In: Human Molecular Genetics. 2016 ; Vol. 25, No. 21. pp. 4717-4725.
@article{78732dccf6264706b6ef7214bddc9e4c,
title = "A critical examination of the recently reported crystal structures of the human SMN protein",
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 froma crystal of the bacterial Sm-like protein Hfq and that a second dataset is derived froma crystal of the bacterial Gab protein. Both proteins are frequent contaminants of bacterially overexpressed proteins whichmight have been co-purified duringmetal 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 weremade publicly available. The Tudor domain protein SMN has been shown to be a component of the SMN complex, whichmediates 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 RNAmetabolism. Structural studies on diverse components of the SMN complex, including fragments of SMN itself have contributed greatly to our understanding of the cellular UsnRNP assemblymachinery. 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 fromthe literature.",
author = "Weiss, {Manfred S.} and Kay Diederichs and Read, {Randy J.} and Santosh Panjikar and {Van Duyne}, {Gregory D.} and Matera, {A. Gregory} and Utz Fischer and Clemens Grimm",
year = "2016",
month = "11",
doi = "10.1093/hmg/ddw298",
language = "English",
volume = "25",
pages = "4717--4725",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "21",

}

Weiss, MS, Diederichs, K, Read, RJ, Panjikar, S, Van Duyne, GD, Matera, AG, Fischer, U & Grimm, C 2016, 'A critical examination of the recently reported crystal structures of the human SMN protein', Human Molecular Genetics, vol. 25, no. 21, pp. 4717-4725. https://doi.org/10.1093/hmg/ddw298

A critical examination of the recently reported crystal structures of the human SMN protein. / Weiss, Manfred S.; Diederichs, Kay; Read, Randy J.; Panjikar, Santosh; Van Duyne, Gregory D.; Matera, A. Gregory; Fischer, Utz; Grimm, Clemens.

In: Human Molecular Genetics, Vol. 25, No. 21, 11.2016, p. 4717-4725.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A critical examination of the recently reported crystal structures of the human SMN protein

AU - Weiss, Manfred S.

AU - Diederichs, Kay

AU - Read, Randy J.

AU - Panjikar, Santosh

AU - Van Duyne, Gregory D.

AU - Matera, A. Gregory

AU - Fischer, Utz

AU - Grimm, Clemens

PY - 2016/11

Y1 - 2016/11

N2 - 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 froma crystal of the bacterial Sm-like protein Hfq and that a second dataset is derived froma crystal of the bacterial Gab protein. Both proteins are frequent contaminants of bacterially overexpressed proteins whichmight have been co-purified duringmetal 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 weremade publicly available. The Tudor domain protein SMN has been shown to be a component of the SMN complex, whichmediates 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 RNAmetabolism. Structural studies on diverse components of the SMN complex, including fragments of SMN itself have contributed greatly to our understanding of the cellular UsnRNP assemblymachinery. 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 fromthe literature.

AB - 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 froma crystal of the bacterial Sm-like protein Hfq and that a second dataset is derived froma crystal of the bacterial Gab protein. Both proteins are frequent contaminants of bacterially overexpressed proteins whichmight have been co-purified duringmetal 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 weremade publicly available. The Tudor domain protein SMN has been shown to be a component of the SMN complex, whichmediates 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 RNAmetabolism. Structural studies on diverse components of the SMN complex, including fragments of SMN itself have contributed greatly to our understanding of the cellular UsnRNP assemblymachinery. 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 fromthe literature.

UR - http://www.scopus.com/inward/record.url?scp=85014812775&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddw298

DO - 10.1093/hmg/ddw298

M3 - Article

VL - 25

SP - 4717

EP - 4725

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 21

ER -