Structure of Aeropyrum pernix fibrillarin in complex with natively bound S-adenosyl-L-methionine at 1.7â
Å resolution.
Acta Crystallogr Sect F Struct Biol Cryst Commun
; 68(Pt 8): 854-9, 2012 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-22869109
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 1.7â
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
S-Adenosilmetionina
/
Proteínas Cromossômicas não Histona
/
Aeropyrum
Idioma:
En
Revista:
Acta Crystallogr Sect F Struct Biol Cryst Commun
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos