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Structure of Aeropyrum pernix fibrillarin in complex with natively bound S ‐adenosyl‐ l ‐methionine at 1.7 Å resolution

Structure of Aeropyrum pernix fibrillarin in complex with natively bound S ‐adenosyl‐ l... Fibrillarin is the key methyltransferase associated with the C/D class of small nuclear ribonucleoproteins (snRNPs) and participates in the preliminary step of pre‐ribosomal rRNA processing. This molecule is found in the fibrillar regions of the eukaryotic nucleolus and is involved in methylation of the 2′‐O atom of ribose in rRNA. Human fibrillarin contains an N‐terminal GAR domain, a central RNA‐binding domain comprising an RNP‐2‐like superfamily consensus sequence and a catalytic C‐terminal helical domain. Here, Aeropyrum pernix fibrillarin is described, which is homologous to the C‐terminal domain of human fibrillarin. The protein was crystallized with an S‐adenosyl‐l‐methionine (SAM) ligand bound in the active site. The molecular structure of this complex was solved using X‐ray crystallography at a resolution of 1.7 Å using molecular replacement with fibrillarin structural homologs. The structure shows the atomic details of SAM and its active‐site interactions; there are a number of conserved residues that interact directly with the cofactor. Notably, the adenine ring of SAM is stabilized by π–π interactions with the conserved residue Phe110 and by electrostatic interactions with the Asp134, Ala135 and Gln157 residues. The π–π interaction appears to play a critical role in stabilizing the association of SAM with fibrillarin. Furthermore, comparison of A. pernix fibrillarin with homologous structures revealed different orientations of Phe110 and changes in α‐helix 6 of fibrillarin and suggests key differences in its interactions with the adenine ring of SAM in the active site and with the C/D RNA. These differences may play a key role in orienting the SAM ligand for catalysis as well as in the assembly of other ribonucleoproteins and in the interactions with C/D RNA. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Acta Crystallographica Section F Wiley

Structure of Aeropyrum pernix fibrillarin in complex with natively bound S ‐adenosyl‐ l ‐methionine at 1.7 Å resolution

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References (24)

Publisher
Wiley
Copyright
International Union of Crystallography, 2012
ISSN
1744-3091
eISSN
1744-3091
DOI
10.1107/S1744309112026528
pmid
22869109
Publisher site
See Article on Publisher Site

Abstract

Fibrillarin is the key methyltransferase associated with the C/D class of small nuclear ribonucleoproteins (snRNPs) and participates in the preliminary step of pre‐ribosomal rRNA processing. This molecule is found in the fibrillar regions of the eukaryotic nucleolus and is involved in methylation of the 2′‐O atom of ribose in rRNA. Human fibrillarin contains an N‐terminal GAR domain, a central RNA‐binding domain comprising an RNP‐2‐like superfamily consensus sequence and a catalytic C‐terminal helical domain. Here, Aeropyrum pernix fibrillarin is described, which is homologous to the C‐terminal domain of human fibrillarin. The protein was crystallized with an S‐adenosyl‐l‐methionine (SAM) ligand bound in the active site. The molecular structure of this complex was solved using X‐ray crystallography at a resolution of 1.7 Å using molecular replacement with fibrillarin structural homologs. The structure shows the atomic details of SAM and its active‐site interactions; there are a number of conserved residues that interact directly with the cofactor. Notably, the adenine ring of SAM is stabilized by π–π interactions with the conserved residue Phe110 and by electrostatic interactions with the Asp134, Ala135 and Gln157 residues. The π–π interaction appears to play a critical role in stabilizing the association of SAM with fibrillarin. Furthermore, comparison of A. pernix fibrillarin with homologous structures revealed different orientations of Phe110 and changes in α‐helix 6 of fibrillarin and suggests key differences in its interactions with the adenine ring of SAM in the active site and with the C/D RNA. These differences may play a key role in orienting the SAM ligand for catalysis as well as in the assembly of other ribonucleoproteins and in the interactions with C/D RNA.

Journal

Acta Crystallographica Section F – Wiley

Published: Aug 1, 2012

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