Identification of functional residues on Caenorhabditis elegans actin-interacting protein 1 (UNC-78) for disassembly of actin depolymerizing factor/cofilin-bound actin filaments

Kurato Mohri, Sergeui Vorobiev, Alexander A. Fedorov, Steven C. Almo, Shoichiro Ono

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Actin-interacting protein 1 (AIP1) is a WD40 repeat protein that enhances actin filament disassembly in the presence of actin-depolymerizing factor (ADF)/cofilin. AIP1 also caps the barbed end of ADF/cofilin-bound actin filament. However, the mechanism by which AIP1 interacts with ADF/cofilin and actin is not clearly understood. We determined the crystal structure of Caenorhabditis elegans AIP1 (UNC-78), which revealed 14 WD40 modules arranged in two seven-bladed β-propeller domains. The structure allowed for the mapping of conserved surface residues, and mutagenesis studies identified five residues that affected the ADF/cofilin-dependent actin filament disassembly activity. Mutations of these residues, which reside in blades 3 and 4 in the N-terminal propeller domain, had significant effects on the disassembly activity but did not alter the barbed end capping activity. These data support a model in which this conserved surface of AIP1 plays a direct role in enhancing fragmentation/depolymerization of ADF/cofilin-bound actin filaments but not in barbed end capping.

Original languageEnglish (US)
Pages (from-to)31697-31707
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number30
DOIs
StatePublished - Jul 23 2004

Fingerprint

Destrin
Actin Depolymerizing Factors
Caenorhabditis elegans
Actin Cytoskeleton
Actins
Propellers
Mutagenesis
Depolymerization
Crystal structure
actin interacting protein 1
Mutation
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of functional residues on Caenorhabditis elegans actin-interacting protein 1 (UNC-78) for disassembly of actin depolymerizing factor/cofilin-bound actin filaments. / Mohri, Kurato; Vorobiev, Sergeui; Fedorov, Alexander A.; Almo, Steven C.; Ono, Shoichiro.

In: Journal of Biological Chemistry, Vol. 279, No. 30, 23.07.2004, p. 31697-31707.

Research output: Contribution to journalArticle

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abstract = "Actin-interacting protein 1 (AIP1) is a WD40 repeat protein that enhances actin filament disassembly in the presence of actin-depolymerizing factor (ADF)/cofilin. AIP1 also caps the barbed end of ADF/cofilin-bound actin filament. However, the mechanism by which AIP1 interacts with ADF/cofilin and actin is not clearly understood. We determined the crystal structure of Caenorhabditis elegans AIP1 (UNC-78), which revealed 14 WD40 modules arranged in two seven-bladed β-propeller domains. The structure allowed for the mapping of conserved surface residues, and mutagenesis studies identified five residues that affected the ADF/cofilin-dependent actin filament disassembly activity. Mutations of these residues, which reside in blades 3 and 4 in the N-terminal propeller domain, had significant effects on the disassembly activity but did not alter the barbed end capping activity. These data support a model in which this conserved surface of AIP1 plays a direct role in enhancing fragmentation/depolymerization of ADF/cofilin-bound actin filaments but not in barbed end capping.",
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