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PMID:18981218

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Citation

Hsiao, YY, Nakagawa, A, Shi, Z, Mitani, S, Xue, D and Yuan, HS (2009) Crystal structure of CRN-4: implications for domain function in apoptotic DNA degradation. Mol. Cell. Biol. 29:448-57

Abstract

Cell death related nuclease 4 (CRN-4) is one of the apoptotic nucleases involved in DNA degradation in Caenorhabditis elegans. To understand how CRN-4 is involved in apoptotic DNA fragmentation, we analyzed CRN-4's biochemical properties, in vivo cell functions, and the crystal structures of CRN-4 in apo-form, Mn(2+)-bound active form, and Er(3+)-bound inactive form. CRN-4 is a dimeric nuclease with the optimal enzyme activity in cleaving double-stranded DNA in apoptotic salt conditions. Both mutational studies and the structures of the Mn(2+)-bound CRN-4 revealed the geometry of the functional nuclease active site in the N-terminal DEDDh domain. The C-terminal domain, termed the Zn-domain, contains basic surface residues ideal for nucleic acid recognition and is involved in DNA binding, as confirmed by deletion assays. Cell death analysis in C. elegans further demonstrated that both the nuclease active site and the Zn-domain are required for crn-4's function in apoptosis. Combining all of the data, we suggest a structural model where chromosomal DNA is bound at the Zn-domain and cleaved at the DEDDh nuclease domain in CRN-4 when the cell is undergoing apoptosis.

Links

PubMed PMC2612515 Online version:10.1128/MCB.01006-08

Keywords

Amino Acid Motifs; Animals; Apoptosis/physiology; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/metabolism; Calcium/metabolism; Catalytic Domain; Crystallography, X-Ray; DNA Fragmentation; DNA, Helminth/metabolism; Dimerization; Endodeoxyribonucleases/chemistry; Endodeoxyribonucleases/metabolism; Endonucleases/chemistry; Endonucleases/metabolism; Hydrogen-Ion Concentration; Magnesium/metabolism; Models, Molecular; Protein Conformation; Protein Structure, Tertiary; Zinc/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:CRN4

enables

GO:0003697: single-stranded DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:CRN4

enables

GO:0008408: 3'-5' exonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:CRN4

enables

GO:0004520: endodeoxyribonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:CRN4

enables

GO:0004540: ribonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:CRN4

involved_in

GO:0006401: RNA catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CRN4

involved_in

GO:0000737: DNA catabolic process, endonucleolytic

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CRN4

involved_in

GO:0000738: DNA catabolic process, exonucleolytic

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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