Solution structure of coactosin reveals structural homology to ADF/cofilin family proteins

Hellman, Maarit; Paavilainen, Ville O.; Naumanen, Perttu; Lappalainen, Pekka; Annila, Arto; Permi, Perttu

doi:10.1016/j.febslet.2004.08.068

Cited by 21 publications

(19 citation statements)

References 35 publications

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“…Class III. The mouse coactosin-like structure is very similar to that of mouse coactosin (PDB id, 1WM4) 19 and to the six other coactosin and coactosin-like structures in the PDB (all from human). The most striking difference is the appearance of an additional b-strand at the N-terminus (Figs.…”

Section: Description Of the Structures And Comparison With Published mentioning

confidence: 68%

NMR solution structures of actin depolymerizing factor homology domains

Goroncy¹,

Koshiba²,

Tochio³

et al. 2009

Protein Science

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Actin is one of the most conserved proteins in nature. Its assembly and disassembly are regulated by many proteins, including the family of actin-depolymerizing factor homology (ADF-H) domains. ADF-H domains can be divided into five classes: ADF/cofilin, glia maturation factor (GMF), coactosin, twinfilin, and Abp1/drebrin. The best-characterized class is ADF/cofilin. The other four classes have drawn much less attention and very few structures have been reported. This study presents the solution NMR structure of the ADF-H domain of human HIP-55-drebrin-like protein, the first published structure of a drebrin-like domain (mammalian), and the first published structure of GMF b (mouse). We also determined the structures of mouse GMF c, the mouse coactosin-like domain and the C-terminal ADF-H domain of mouse twinfilin 1. Although the overall fold of the five domains is similar, some significant differences provide valuable insights into filamentous actin (F-actin) and globular actin (G-actin) binding, including the identification of binding residues on the long central helix. This long helix is stabilized by three or four residues. Notably, the F-actin binding sites of mouse GMF b and GMF c contain two additional b-strands not seen in other ADF-H structures. The G-actin binding site of the ADF-H domain of human HIP-55-drebrin-like protein is absent and distorted in mouse GMF b and GMF c.

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Section: Description Of the Structures And Comparison With Published mentioning

confidence: 68%

NMR solution structures of actin depolymerizing factor homology domains

Goroncy¹,

Koshiba²,

Tochio³

et al. 2009

Protein Science

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“…With the exception of D. discoideum coactosin, which weakly interferes with barbedend capping of actin filaments (68), coactosins do not seem to promote actin filament elongation or disassembly. It has been suggested that, in vivo, coactosins regulate actin dynamics as a member of a complex with other proteins (69). EhCoactosin possesses an ADF-H domain; however, it remains to be seen if it binds actin and if it has additional interacting protein partners.…”

Section: Fig 8 Gfp-phmentioning

confidence: 99%

A Genomewide Overexpression Screen Identifies Genes Involved in the Phosphatidylinositol 3-Kinase Pathway in the Human Protozoan Parasite Entamoeba histolytica

et al. 2014

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Entamoeba histolytica is a protozoan parasite that causes amoebic dysentery and liver abscess. E. histolytica relies on motility, phagocytosis, host cell adhesion, and proteolysis of extracellular matrix for virulence. In eukaryotic cells, these processes are mediated in part by phosphatidylinositol 3-kinase (PI3K) signaling. Thus, PI3K may be critical for virulence. We utilized a functional genomics approach to identify genes whose products may operate in the PI3K pathway in E. histolytica. We treated a population of trophozoites that were overexpressing genes from a cDNA library with a near-lethal dose of the PI3K inhibitor wortmannin. This screen was based on the rationale that survivors would be overexpressing gene products that directly or indirectly function in the PI3K pathway. We sequenced the overexpressed genes in survivors and identified a cDNA encoding a Rap GTPase, a protein previously shown to participate in the PI3K pathway. This supports the validity of our approach. Genes encoding a coactosin-like protein, EhCoactosin, and a serine-rich E. histolytica protein (SREHP) were also identified. Cells overexpressing EhCoactosin or SREHP were also less sensitive to a second PI3K inhibitor, LY294002. This corroborates the link between these proteins and PI3K. Finally, a mutant cell line with an increased level of phosphatidylinositol (3,4,5)-triphosphate, the product of PI3K activity, exhibited increased expression of SREHP and EhCoactosin. This further supports the functional connection between these proteins and PI3K in E. histolytica. To our knowledge, this is the first forward-genetics screen adapted to reveal genes participating in a signal transduction pathway in this pathogen. E ntamoeba histolytica is an enteric protozoan parasite that causes amoebiasis and amoebic liver abscess in humans (1). It is prevalent in developing countries that cannot prevent its fecaloral spread. E. histolytica enters the human host upon ingestion of water or food contaminated with environmentally stable cysts. After passing through the stomach, excystation leads to the release of trophozoites, which migrate to the bowel lumen for colonization. In 10% of infected individuals, infection can progress from a noninvasive stage to an invasive stage (2), during which the parasite binds to and destroys colonic epithelium. From here, the parasites enter the circulatory system and translocate to other organs. The most common site of extraintestinal infection is the liver, characterized by the formation of amebic liver abscess (ALA).E. histolytica relies on cell motility, phagocytosis, proteolysis of host extracellular matrix, and host cell adhesion for virulence (3). In other eukaryotic cells, these processes are mediated in part by phosphatidylinositol 3-kinase (PI3K) signaling (4). PI3Ks phosphorylate phosphatidylinositol (PI) and its derivatives to generate signaling lipids such as phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 3,4-bisphosphate [PI(3,4)P 2 ], phosphatidylinositol 3,5-bisphosphate [PI(3,5)P 2 ]...

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“…The only signifi cant structural change was observed in the two N-terminal residues of Twf-C (residues 176 -177), which are part of a fl exible extension in most ADF-H domain structures without actin ( Paavilainen et al, , 2007Hellman et al, 2004 ;Quintero-Monzon et al, 2005 ;Andrianantoandro and Pollard, 2006 ), but become ordered in complex with actin and form an important part of the interaction surface (see following paragraph).…”

Section: Introductionmentioning

confidence: 99%

Structure of the actin-depolymerizing factor homology domain in complex with actin

Paavilainen

Oksanen

Goldman

et al. 2008

The Journal of Cell Biology

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176

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Abbreviations used in this paper: ADF-H, actin-depolymerizing factor homology; NBD, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole; WH2, WASP homology 2.The online version of this paper contains supplemental material. IntroductionPolymerization of actin fi laments against membranes produces pushing forces that are required for various cellular processes such as motility, morphogenesis, and endocytosis ( Pollard and Borisy, 2003 ;Kaksonen et al., 2006 ). Despite the large number of proteins regulating actin dynamics, many of them interact with actin through a relatively small number of protein domains. Among the central actin-binding domains is the actin-depolymerizing factor homology (ADF-H) domain, which occurs in five functionally distinct classes of proteins: ADF/cofilin, twinfi lin, Abp1/drebrin, coactosin, and glia maturation factor ( Paavilainen et al., 2007 ).The founding member of this family, ADF/cofi lin, binds both monomeric and fi lamentous actin, preferably in the ADPbound form, and induces a structural rearrangement in the actin fi lament that leads to its disassembly. When bound to an actin monomer, ADF/cofi lin inhibits spontaneous nucleotide exchange ( Carlier et al., 1997 ;Bamburg, 1999 ;Andrianantoandro and Pollard, 2006 ). In cells, ADF/cofi lin plays an essential role in various processes by promoting disassembly of aged actin fi laments ( Okreglak and Drubin, 2007 ). In contrast to ADF/cofi lin, which consists of a single ADF-H domain, twinfi lin is composed of two ADF-H domains separated by a short linker region . Twinfi lin binds ADP-actin monomers and fi lament barbed ends with high affi nity, and prevents monomer assembly into fi lament ends Helfer et al., 2006 ). In addition, yeast twinfi lin induces fi lament severing at a low pH ( Moseley et al., 2006 ). Biochemical studies suggested that during barbedend capping, twinfi lin ' s N-terminal ADF-H domain interacts with the terminal actin subunit, whereas the C-terminal ADF-H domain binds to the side of an actin fi lament through a similar mechanism to that of ADF/cofi lin ( Paavilainen et al., 2007 ). The exact functions of the Abp1/drebrin, coactosin, and glia maturation factor are less well understood, although also these proteins are linked to regulation of actin dynamics ( de Hostos et al., 1993 ;Quintero-Monzon et al., 2005 ;Ikeda et al., 2006 ).Although the biochemical activities and cellular functions of ADF-H domain proteins are rapidly being uncovered, the structure of an ADF-H domain in complex with actin has not been reported. Indirect structural methods have provided controversial results, and even the binding site of this domain on actin is not known ( Wriggers et al., 1998 ;Kamal et al., 2007 ). Consequently, the structural mechanisms by which twinfi lin and ADF/cofi lin inhibit nucleotide exchange on actin monomers and how ADF/cofi lin induces fi lament depolymerization/ severing are unknown.A ctin dynamics provide the driving force for many cellular processes including motility and endocytosis. Among the central cytoskeletal re...

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Solution structure of coactosin reveals structural homology to ADF/cofilin family proteins

Cited by 21 publications

References 35 publications

NMR solution structures of actin depolymerizing factor homology domains

NMR solution structures of actin depolymerizing factor homology domains

A Genomewide Overexpression Screen Identifies Genes Involved in the Phosphatidylinositol 3-Kinase Pathway in the Human Protozoan Parasite Entamoeba histolytica

Structure of the actin-depolymerizing factor homology domain in complex with actin

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