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Human lysosomal DNase IIalpha contains two requisite PLD-signature (HxK) motifs: evidence for a pseudodimeric structure of the active enzyme species.

ABSTRACT: Lysosomal DNase IIalpha is essential for DNA waste removal and auxiliary apoptotic DNA fragmentation in higher eukaryotes. Despite the key role of this enzyme, little is known about its structure-function relationships. Here, mutational and biochemical analyses were used to characterize human DNase IIalpha variants expressed in mammalian cells. The resulting data strongly support the hypothesis that the enzyme is a monomeric phospholipase D-family member with a pseudodimeric protein fold. According to our results, DNase IIalpha contains two requisite PLD-signature motifs ((113)HTK(115) and (295)HSK(297)) in the N- and C-terminal subdomains, respectively, that together form a single active site. Based on these data, we present an experimentally validated structural model of DNase IIalpha.

SUBMITTER: Schafer P

PROVIDER: S-EPMC2222834 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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Human lysosomal DNase IIalpha contains two requisite PLD-signature (HxK) motifs: evidence for a pseudodimeric structure of the active enzyme species.

Schäfer Patrick P Cymerman Iwona A IA Bujnicki Janusz M JM Meiss Gregor G

Protein science : a publication of the Protein Society 20070101 1

Lysosomal DNase IIalpha is essential for DNA waste removal and auxiliary apoptotic DNA fragmentation in higher eukaryotes. Despite the key role of this enzyme, little is known about its structure-function relationships. Here, mutational and biochemical analyses were used to characterize human DNase IIalpha variants expressed in mammalian cells. The resulting data strongly support the hypothesis that the enzyme is a monomeric phospholipase D-family member with a pseudodimeric protein fold. Accord ...[more]

PMID: 17192590

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