Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain

Ke Liu, Chen Chen, Yahong Guo, Robert Lam, Chuanbing Bian, Chao Xu, Dorothy Y. Zhao, Jing Jin, Farrell MacKenzie, Tony Pawson*, Jinrong Min

*Corresponding author for this work

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Arginine methylation modulates diverse cellular processes and represents a molecular signature of germ-line-specific Piwi family proteins.Asubset of Tudor domains recognize arginine methylation modifications, but the binding mechanism has been lacking. Here we establish that, like other germ-line Tudor proteins, the ancestral staphylococcal nuclease domain-containing 1 (SND1) polypeptide is expressed and associates with PIWIL1/Miwi in germ cells. We find that human SND1 binds PIWIL1 in an arginine methylation-dependent manner with a preference for symmetrically dimethylated arginine. The entire Tudor domain and a bifurcated SN domain are required for this binding activity, whereas the canonical Tudor domain alone is insufficient for methylarginine ligand binding. Crystal structures show that the intact SND1 extended Tudor domain forms a wide and negatively charged binding groove, which can accommodate distinct symmetrically dimethylated arginine peptides from PIWIL1 in different orientations. This analysis explains how SND1 preferentially recognizes symmetrical dimethylarginine via an aromatic cage and conserved hydrogen bonds, and provides a general paradigm for the binding mechanisms of methylarginine-containing peptides by extended Tudor domains.

Original languageEnglish (US)
Pages (from-to)18398-18403
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number43
DOIs
StatePublished - Oct 26 2010

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Micrococcal Nuclease
Arginine
Germ Cells
Methylation
Proteins
Peptides
Hydrogen
Tudor Domain
Ligands

Keywords

  • Piwi-interacting RNA
  • Tudor domain-containing proteins

ASJC Scopus subject areas

  • General

Cite this

Liu, Ke ; Chen, Chen ; Guo, Yahong ; Lam, Robert ; Bian, Chuanbing ; Xu, Chao ; Zhao, Dorothy Y. ; Jin, Jing ; MacKenzie, Farrell ; Pawson, Tony ; Min, Jinrong. / Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 43. pp. 18398-18403.
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Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain. / Liu, Ke; Chen, Chen; Guo, Yahong; Lam, Robert; Bian, Chuanbing; Xu, Chao; Zhao, Dorothy Y.; Jin, Jing; MacKenzie, Farrell; Pawson, Tony; Min, Jinrong.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 43, 26.10.2010, p. 18398-18403.

Research output: Contribution to journalArticle

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T1 - Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain

AU - Liu, Ke

AU - Chen, Chen

AU - Guo, Yahong

AU - Lam, Robert

AU - Bian, Chuanbing

AU - Xu, Chao

AU - Zhao, Dorothy Y.

AU - Jin, Jing

AU - MacKenzie, Farrell

AU - Pawson, Tony

AU - Min, Jinrong

PY - 2010/10/26

Y1 - 2010/10/26

N2 - Arginine methylation modulates diverse cellular processes and represents a molecular signature of germ-line-specific Piwi family proteins.Asubset of Tudor domains recognize arginine methylation modifications, but the binding mechanism has been lacking. Here we establish that, like other germ-line Tudor proteins, the ancestral staphylococcal nuclease domain-containing 1 (SND1) polypeptide is expressed and associates with PIWIL1/Miwi in germ cells. We find that human SND1 binds PIWIL1 in an arginine methylation-dependent manner with a preference for symmetrically dimethylated arginine. The entire Tudor domain and a bifurcated SN domain are required for this binding activity, whereas the canonical Tudor domain alone is insufficient for methylarginine ligand binding. Crystal structures show that the intact SND1 extended Tudor domain forms a wide and negatively charged binding groove, which can accommodate distinct symmetrically dimethylated arginine peptides from PIWIL1 in different orientations. This analysis explains how SND1 preferentially recognizes symmetrical dimethylarginine via an aromatic cage and conserved hydrogen bonds, and provides a general paradigm for the binding mechanisms of methylarginine-containing peptides by extended Tudor domains.

AB - Arginine methylation modulates diverse cellular processes and represents a molecular signature of germ-line-specific Piwi family proteins.Asubset of Tudor domains recognize arginine methylation modifications, but the binding mechanism has been lacking. Here we establish that, like other germ-line Tudor proteins, the ancestral staphylococcal nuclease domain-containing 1 (SND1) polypeptide is expressed and associates with PIWIL1/Miwi in germ cells. We find that human SND1 binds PIWIL1 in an arginine methylation-dependent manner with a preference for symmetrically dimethylated arginine. The entire Tudor domain and a bifurcated SN domain are required for this binding activity, whereas the canonical Tudor domain alone is insufficient for methylarginine ligand binding. Crystal structures show that the intact SND1 extended Tudor domain forms a wide and negatively charged binding groove, which can accommodate distinct symmetrically dimethylated arginine peptides from PIWIL1 in different orientations. This analysis explains how SND1 preferentially recognizes symmetrical dimethylarginine via an aromatic cage and conserved hydrogen bonds, and provides a general paradigm for the binding mechanisms of methylarginine-containing peptides by extended Tudor domains.

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