Structural basis for dimethylarginine recognition by the Tudor domains of human SMN and SPF30 proteins

Tripsianes, Konstantinos; Madl, Tobias; Machyna, Martin; Fessas, Dimitrios; Englbrecht, Clemens; Fischer, Utz; Neugebauer, Karla M.; Sattler, Michael

doi:10.1038/nsmb.2185

Cited by 175 publications

(210 citation statements)

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“…In addition, some tudor domains recognize methylated arginine residues of histone and nonhistone proteins (16)(17)(18)(19)(20). These methylation-dependent interactions impact a wide spectrum of biological processes in eukaryotes.…”

Section: Discussionmentioning

confidence: 99%

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1

Yang

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Recognition of methylated histone tail lysine residues by tudor domains plays important roles in epigenetic control of gene expression and DNA damage response. Previous studies revealed the binding of methyllysine in a cage of aromatic residues, but the molecular mechanism by which the sequence specificity for surrounding histone tail residues is achieved remains poorly understood. In the crystal structure of a trimethylated histone H3 lysine 4 (H3K4) peptide bound to the tudor-like domains of Spindlin1 presented here, an atypical mode of methyllysine recognition by an aromatic pocket of Spindlin1 is observed. Furthermore, the histone sequence is recognized in a distinct manner involving the amino terminus and a pair of arginine residues of histone H3, and disruption of the binding impaired stimulation of pre-RNA expression by Spindlin1. Our analysis demonstrates considerable diversities of methyllysine recognition and sequence-specific binding of histone tails by tudor domains, and the revelation furthers the understanding of tudor domain proteins in deciphering epigenetic marks on histone tails.H istone lysine methylation imparts epigenetic information in chromatin biology, and the transduction of epigenetic signal is mediated by a diverse group of proteins containing methyllysine recognition domains (1). Some of the best known methyllysine recognition modules include chromo, tudor, MBT (Malignant Brain Tumor), and PHD (Plant Homeodomain) domains (2-4). A recent addition of this family of histone methyllysine "readers" is the BAH domain ORC1 (5). These methyllysine "readers" can recognize histone lysine methylation in a site-specific and methylation state-specific manner. A common feature of methyllysine recognitions involves a cage of aromatic residues, whereas the ways for discriminating the surrounding amino acid sequence of histones appear to be divergent among different methyllysine "readers." In this study, we focus on the recognition of trimethylated lysine-4 of histone H3 (H3K4me3) by the tandem tudor-like domains of Spindlin1.Mammalian Spindlin1 is a nucleolar protein that localizes to the active ribosomal DNA (rDNA) repeats locus, where it is normally enriched with histone H3K4 and H3K36 methylations, and facilitates rRNA expression (6, 7). Spindlin1 contains three tandem tudor-like domains (8), and we previously demonstrated that the tudor-like domains bind to H3K4me3 in vitro (7). Furthermore, Spindlin1 mutants with impaired H3K4me3 binding showed reduced stimulation of rRNA expression (7). Hence, these observations directly link the ability of H3K4me3 binding with the transcription function of Spindlin1. However, several important aspects of the molecular mechanism of H3K4me3 recognition by Spindlin1 remain outstanding; foremost ones include how Spindlin1 achieves its H3K4me3 specificity and what features distinguish the H3K4me3-binding tudor-like domain from others in Spindlin1. Previous structural studies of tudor domains have yielded some understandings of how they recognize methylated histone ...

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Section: Discussionmentioning

confidence: 99%

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1

Yang

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…G.M., unpublished observations). Structural analysis of the SMN Tudor domain has also been carried out, 35,103 revealing the existence of an "aromatic cage" of b-sheets that mediates recognition of dimethylarginine residues present on Sm proteins. Future studies will be required to determine how these 2 regions, as well as the a-helical Gemin2 (Gem2) binding domain at the N-terminus 50,104 all fit together in space to carry out SMN's various functions.…”

Section: Oligomeric Properties Of Smn Complexesmentioning

confidence: 99%

“…[34][35][36][37] The Sm-class snRNPs consist of uridine-rich snRNAs (e.g. U1, U2, U4, U5), several specific proteins that are unique to each snRNA, and a set of 7 common Sm proteins (B/ B', D1, D2, D3, E, F, and G).…”

Section: Smn and Cytoplasmic Snrnp Assemblymentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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Survival Motor Neuron (SMN) protein localizes to both the nucleus and the cytoplasm. Cytoplasmic SMN is diffusely localized in large oligomeric complexes with core member proteins, called Gemins. Biochemical and cell biological studies have demonstrated that the SMN complex is required for the cytoplasmic assembly and nuclear transport of Sm-class ribonucleoproteins (RNPs). Nuclear SMN accumulates with spliceosomal small nuclear (sn)RNPs in Cajal bodies, sub-domains involved in multiple facets of snRNP maturation. Thus, the SMN complex forms stable associations with both nuclear and cytoplasmic snRNPs, and plays a critical role in their biogenesis. In this review, we focus on potential functions of the nuclear SMN complex, with particular emphasis on its role within the Cajal body.

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“…Specific binding via a trimethylammonium moiety, such as that found in PC headgroups, has been observed in proteins that bind proline betaine and glycine betaine (11,12) or choline (13,14) as well as proteins that bind methylated lysine in histones (15)(16)(17) or methylated arginine (18). In these structures, the methylammonium is the center of a cationbox with the faces of 2 to 4 aromatic residues located within 4 -5 Å of the methylated amine allowing cation-interactions with the aromatic residues.…”

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confidence: 99%