Recognition of 2'-O-methylated 3'-end of piRNA by the PAZ domain of a Piwi protein

Bernd Simon; John P Kirkpatrick; Stephanie Eckhardt; Michael Reuter; Elsa A Rocha; Miguel A Andrade-Navarro; Peter Sehr; Ramesh S Pillai; Teresa Carlomagno

doi:10.1016/j.str.2010.11.015

Recognition of 2'-O-methylated 3'-end of piRNA by the PAZ domain of a Piwi protein

Bernd Simon, John P Kirkpatrick, Stephanie Eckhardt, Michael Reuter, Elsa A Rocha, Miguel A Andrade-Navarro, Peter Sehr, Ramesh S Pillai, Teresa Carlomagno

Biosciences

Research output: Contribution to journal › Article › peer-review

Abstract

Piwi proteins are germline-specific Argonautes that associate with small RNAs called Piwi-interacting RNAs (piRNAs), and together with these RNAs are implicated in transposon silencing. The PAZ domain of Argonaute proteins recognizes the 3'-end of the RNA, which in the case of piRNAs is invariably modified with a 2'-O-methyl group. Here, we present the solution structure of the PAZ domain from the mouse Piwi protein, MIWI, in complex with an 8-mer piRNA mimic. The methyl group is positioned in a hydrophobic cavity made of conserved amino acids from strand β7 and helix α3, where it is contacted by the side chain of methionine-382. Our structure is similar to that of Ago-PAZ, but subtle differences illustrate how the PAZ domain has evolved to accommodate distinct 3' ends from a variety of RNA substrates.

Original language	English
Pages (from-to)	172-80
Number of pages	9
Journal	Structure
Volume	19
Issue number	2
DOIs	https://doi.org/10.1016/j.str.2010.11.015
Publication status	Published - 9 Feb 2011

Bibliographical note

Keywords

Amino Acid Sequence
Animals
Argonaute Proteins
Binding Sites
DNA Transposable Elements
Escherichia coli
Evolution, Molecular
Gene Silencing
Methionine/metabolism
Methylation
Mice
Molecular Mimicry/genetics
Molecular Sequence Data
Oligonucleotides/chemical synthesis
Protein Binding
Protein Structure, Tertiary
Proteins/genetics
RNA, Small Interfering/genetics
Recombinant Proteins/genetics
Surface Plasmon Resonance

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10.1016/j.str.2010.11.015

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title = "Recognition of 2'-O-methylated 3'-end of piRNA by the PAZ domain of a Piwi protein",

abstract = "Piwi proteins are germline-specific Argonautes that associate with small RNAs called Piwi-interacting RNAs (piRNAs), and together with these RNAs are implicated in transposon silencing. The PAZ domain of Argonaute proteins recognizes the 3'-end of the RNA, which in the case of piRNAs is invariably modified with a 2'-O-methyl group. Here, we present the solution structure of the PAZ domain from the mouse Piwi protein, MIWI, in complex with an 8-mer piRNA mimic. The methyl group is positioned in a hydrophobic cavity made of conserved amino acids from strand β7 and helix α3, where it is contacted by the side chain of methionine-382. Our structure is similar to that of Ago-PAZ, but subtle differences illustrate how the PAZ domain has evolved to accommodate distinct 3' ends from a variety of RNA substrates.",

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author = "Bernd Simon and Kirkpatrick, {John P} and Stephanie Eckhardt and Michael Reuter and Rocha, {Elsa A} and Andrade-Navarro, {Miguel A} and Peter Sehr and Pillai, {Ramesh S} and Teresa Carlomagno",

year = "2011",

month = feb,

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doi = "10.1016/j.str.2010.11.015",

language = "English",

volume = "19",

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journal = "Structure",

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AU - Simon, Bernd

AU - Kirkpatrick, John P

AU - Eckhardt, Stephanie

AU - Reuter, Michael

AU - Rocha, Elsa A

AU - Andrade-Navarro, Miguel A

AU - Sehr, Peter

AU - Pillai, Ramesh S

AU - Carlomagno, Teresa

PY - 2011/2/9

Y1 - 2011/2/9

N2 - Piwi proteins are germline-specific Argonautes that associate with small RNAs called Piwi-interacting RNAs (piRNAs), and together with these RNAs are implicated in transposon silencing. The PAZ domain of Argonaute proteins recognizes the 3'-end of the RNA, which in the case of piRNAs is invariably modified with a 2'-O-methyl group. Here, we present the solution structure of the PAZ domain from the mouse Piwi protein, MIWI, in complex with an 8-mer piRNA mimic. The methyl group is positioned in a hydrophobic cavity made of conserved amino acids from strand β7 and helix α3, where it is contacted by the side chain of methionine-382. Our structure is similar to that of Ago-PAZ, but subtle differences illustrate how the PAZ domain has evolved to accommodate distinct 3' ends from a variety of RNA substrates.

AB - Piwi proteins are germline-specific Argonautes that associate with small RNAs called Piwi-interacting RNAs (piRNAs), and together with these RNAs are implicated in transposon silencing. The PAZ domain of Argonaute proteins recognizes the 3'-end of the RNA, which in the case of piRNAs is invariably modified with a 2'-O-methyl group. Here, we present the solution structure of the PAZ domain from the mouse Piwi protein, MIWI, in complex with an 8-mer piRNA mimic. The methyl group is positioned in a hydrophobic cavity made of conserved amino acids from strand β7 and helix α3, where it is contacted by the side chain of methionine-382. Our structure is similar to that of Ago-PAZ, but subtle differences illustrate how the PAZ domain has evolved to accommodate distinct 3' ends from a variety of RNA substrates.

KW - Amino Acid Sequence

KW - Animals

KW - Argonaute Proteins

KW - Binding Sites

KW - DNA Transposable Elements

KW - Escherichia coli

KW - Evolution, Molecular

KW - Gene Silencing

KW - Methionine/metabolism

KW - Methylation

KW - Mice

KW - Molecular Mimicry/genetics

KW - Molecular Sequence Data

KW - Oligonucleotides/chemical synthesis

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Proteins/genetics

KW - RNA, Small Interfering/genetics

KW - Recombinant Proteins/genetics

KW - Surface Plasmon Resonance

U2 - 10.1016/j.str.2010.11.015

DO - 10.1016/j.str.2010.11.015

M3 - Article

C2 - 21237665

SN - 0969-2126

VL - 19

SP - 172

EP - 180

JO - Structure

JF - Structure

IS - 2

ER -

Recognition of 2'-O-methylated 3'-end of piRNA by the PAZ domain of a Piwi protein

Abstract

Bibliographical note

Keywords

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