RNA specificity and regulation of catalysis in the eukaryotic polynucleotide kinase Clp1.
Mol Cell
; 54(6): 975-986, 2014 Jun 19.
Article
em En
| MEDLINE
| ID: mdl-24813946
ABSTRACT
RNA-specific polynucleotide kinases of the Clp1 subfamily are key components of various RNA maturation pathways. However, the structural basis explaining their substrate specificity and the enzymatic mechanism is elusive. Here, we report crystal structures of Clp1 from Caenorhabditis elegans (ceClp1) in a number of nucleotide- and RNA-bound states along the reaction pathway. The combined structural and biochemical analysis of ceClp1 elucidates the RNA specificity and lets us derive a general model for enzyme catalysis of RNA-specific polynucleotide kinases. We identified an RNA binding motif referred to as "clasp" as well as a conformational switch that involves the essential Walker A lysine (Lys127) and regulates the enzymatic activity of ceClp1. Structural comparison with other P loop proteins, such as kinases, adenosine triphosphatases (ATPases), and guanosine triphosphatases (GTPases), suggests that the observed conformational switch of the Walker A lysine is a broadly relevant mechanistic feature.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
RNA Ligase (ATP)
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Proteínas de Ligação a RNA
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Caenorhabditis elegans
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Fosfotransferases (Aceptor do Grupo Álcool)
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article