4DF3

Crystal Structure of Aeropyrum pernix fibrillarin in complex with natively bound S-adenosyl-L-methionine at 1.7A

Summary for 4DF3

• Entry DOI: 10.2210/pdb4df3/pdb
• Descriptor: Fibrillarin-like rRNA/tRNA 2'-O-methyltransferase, S-ADENOSYLMETHIONINE (3 entities in total)
• Functional Keywords: nadp rossmann superfamily, methyltransferase, s-adenosyl-l-methionine (sam) binding, nucleolus, transferase
• Biological source: Aeropyrum pernix
• Total number of polymer chains: 2
• Total formula weight: 54194.54

Authors

de Silva, U. (deposition date: 2012-01-22, release date: 2012-08-08, Last modification date: 2024-02-28)

Primary citation

de Silva, U.,Zhou, Z.,Brown, B.A.
Structure of Aeropyrum pernix fibrillarin in complex with natively bound S-adenosyl-L-methionine at 1.7 A resolution.
Acta Crystallogr.,Sect.F, 68:854-859, 2012

PubMed 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.

PubMed: 22869109
DOI: 10.1107/S1744309112026528

Experimental method

X-RAY DIFFRACTION (1.73 Å)