The C Terminus of Annexin II Mediates Binding to F-actin

Filipenko, Nolan R.; Waisman, David M.

doi:10.1074/jbc.m009710200

Cited by 114 publications

(109 citation statements)

References 51 publications

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“…Among a large number of PtdIns(4,5)P 2 -binding proteins, A2t is suited for this putative role due to its unique properties; i.e. A2t binds the membrane in a Ca 2ϩ -and/or PtdIns(4,5)P 2 -dependent manner (21,22), laterally aggregates on the membrane surface (14), interacts with F-actin (59), and is abundant in mammalian cells. Furthermore, recent reports have indicated the potential involvement of annexin A2 and A2t in regulation of membrane microdomain formation (15,16).…”

Section: Discussionmentioning

confidence: 99%

Phosphoinositide Specificity of and Mechanism of Lipid Domain Formation by Annexin A2-p11 Heterotetramer

Gokhale

Abraham

Digman

et al. 2005

Journal of Biological Chemistry

104

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Annexin A2 is a phospholipid-binding protein that forms a heterotetramer (annexin II-p11 heterotetramer; A2t) with p11 (S100A10). It has been reported that annexin A2 is involved in binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) and in inducing membrane microdomain formation. To understand the mechanisms underlying these findings, we determined the membrane binding properties of annexin A2 wild type and mutants both as monomer and as A2t. Our results from surface plasmon resonance analysis showed that A2t and annexin A2 has modest selectivity for PtdIns(4,5)P 2 over other phosphoinositides, which is conferred by conserved basic residues, including Lys 279 and Lys 281 , on the convex surface of annexin A2. Fluorescence microscopy measurements using giant unilamellar vesicles showed that A2t of wild type, but not (K279A) 2 -(p11) 2 or (K281A) 2 -(p11) 2 , specifically induced the formation of 1-m-sized PtdIns(4,5)P 2 clusters, which were stabilized by cholesterol. Collectively, these studies elucidate the structural determinant of the PtdIns(4,5)P 2 selectivity of A2t and suggest that A2t may be involved in the regulation of PtdIns(4,5)P 2 clustering in the cell.Annexins are a family of peripheral proteins that bind anionic phospholipids in a Ca 2ϩ -dependent manner (1-5). Structures and in vitro functions of annexins have been well characterized. Annexins have a variable N-terminal region and a conserved C-terminal core that is composed of four (eight in case of annexin A6) ␣-helical annexin folds (2). The C-terminal core is the Ca 2ϩ -dependent membrane-binding module that contains multiple Ca 2ϩ -binding sites on its convex membrane-binding surface (2). The N-terminal region of annexins is attached to the concave side of the C-terminal core and thought to be involved in interactions with other proteins and post-translational modifications (3-5). In addition to their membrane-binding activities, annexins have been reported to have other in vitro activities, including membrane aggregation and lateral aggregation on the membrane surface (6). Despite the wealth of structural and functional information on annexins, their physiological functions are only beginning to emerge with recent genetic and cell studies (3-5).Annexin A2 is an abundant cellular protein that has been implicated in numerous physiological processes (3-5, 7). Annexin A2 interacts with an EF-hand protein p11 (also known as S100A11) with high affinity via its N-terminal region, forming a symmetric heterotetramer, (annexin A2) 2 -(p11) 2 (A2t) 2 (8, 9). Annexin A2 has been reported to exist either as a monomer or A2t in mammalian cells (3, 10 -12). Annexin A2 and A2t have been shown to have high vesicle aggregating activity (13) and form a monolayer of protein clusters when bound to the lipid bilayer with anionic phospholipids accumulating underneath the protein clusters (14). Mounting evidence indicates that annexin A2 and A2t are involved in organizing cholesterol-rich lipid rafts (15, 16) and linking them to cytoskeletal protein...

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Section: Discussionmentioning

confidence: 99%

Phosphoinositide Specificity of and Mechanism of Lipid Domain Formation by Annexin A2-p11 Heterotetramer

Gokhale

Abraham

Digman

et al. 2005

Journal of Biological Chemistry

104

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“…SNX17 resides in distinct parts of the early endosomal compartment and enhances the endocytosis rate of LDLR, and possibly of other surface receptors [25] . The A2IC faces the cytosol and is in ideal proximity to interact with the actin cytoskeleton within the cell [8] . In preclinical tumor models, it has been shown that therapeutic targeting of RPS2 is an excellent approach for the eradication of prostate cancer [26] .…”

Section: Discussionmentioning

confidence: 99%

“…Annexin A2 is cleaved by chymotrypsin and plasmin into a 33 kDa C-terminal core domain and a 3 kDa N-terminal domain. The first 14 residues of the N-terminal domain contain a high-affinity binding site for S100A10, a Ca 2+ binding protein [8,10] (Figure 1). Annexin A2 interacts with S100A10 to form AA2t [11] .…”

Section: Introductionmentioning

confidence: 99%

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Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2

Laumonnier

Syrovets

et al. 2011

Acta Pharmacol Sin

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Aim: To identify proteins that interact with the C-terminal fragment of annexin A2 (A2IC), generated by plasmin cleavage of the plasmin receptor, a heterotetramer (AA2t) containing annexin A2. Methods: The gene that encodes the A2IC fragment was obtained from PCR-amplified cDNA isolated from human monocytes, and was ligated into the pBTM116 vector using a DNA ligation kit. The resultant plasmid (pBTM116-A2IC) was sequenced with an ABI PRISM 310 Genetic Analyzer. The expression of an A2IC bait protein fused with a LexA-DNA binding domain (BD) was determined using Western blot analysis. The identification of proteins that interact with A2IC and are encoded in a human monocyte cDNA library was performed using yeast two-hybrid screening. The DNA sequences of the relevant cDNAs were determined using an ABI PRISM BigDye terminator cycle sequencing ready reaction kit. Nucleotide sequence databases were searched for homologous sequences using BLAST search analysis (http://www.ncbi.nlm.nih.gov). Confirmation of the interaction between the protein LexA-A2IC and each of cathepsin S and SNX17 was conducted using a small-scale yeast transformation and X-gal assay. Results: The yeast transformed with plasmids encoding the bait proteins were screened with a human monocyte cDNA library by reconstituting full-length transcription factors containing the GAL4-active domain (GAL4-AD) as the prey in a yeast two-hybrid approach. After screening 1×10 7 clones, 23 independent β-Gal-positive clones were identified. Sequence analysis and a database search revealed that 15 of these positive clones matched eight different proteins (SNX17, ProCathepsin S, RPS2, ZBTB4, OGDH, CCDC32, PAPD4, and actin which was already known to interact with annexin A2). Conclusion: A2IC A2IC interacts with various proteins to form protein complexes, which may contribute to the molecular mechanism of monocyte activation induced by plasmin. The yeast two-hybrid system is an efficient approach for investigating protein interactions.Keywords: yeast yeast two-hybrid system; human monocyte; plasmin receptor; C-terminal fragment of annexin A2 (A2IC); protein-protein interaction Acta

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“…The protein has been implicated in numerous cellular processes; for example, aggregation of phospholipid vesicles (Blackwood & Ernst, 1990;Ayala-Sanmartin et al, 2001), G-actin polymerization Hayes et al, 2006), F-actin bundling (Filipenko & Waisman, 2001), apical lumen formation (Martin-Belmonte et al, 2007), endosome biogenesis (Morel et al, 2009), angiogenesis (Semov et al, 2005) and exocytosis (Lorusso et al, 2006;Umbrecht-Jenck et al, 2010). Additionally, several unique and diverse binding partners and ligands of AnxA2 have been identified, such as PCSK9 (Mayer et al, 2008), phosphatidylinositol 4,5-bisphosphate (Rescher et al, 2004), heparin , chlorotoxin (Kesavan et al, 2010) and progastrin (Singh et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

Ozorowski

Milton

Luecke

2012

Acta Crystallogr D Biol Crystallogr

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AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2–S100A10 heterotetramer [(p11)2(AnxA2)2)] has high affinity for several regions of its 1002‐amino‐acid C‐terminal domain. (p11)2(AnxA2)2 is often localized near the plasma membrane, and this C2‐symmetric platform is proposed to be involved in the bridging of membrane vesicles and trafficking of proteins to the plasma membrane. All three proteins co‐localize at the intracellular face of the plasma membrane in a Ca2+‐dependent manner. The binding of AHNAK to (p11)2(AnxA2)2 has been studied previously, and a minimal binding motif has been mapped to a 20‐amino‐acid peptide corresponding to residues 5654–5673 of the AHNAK C‐terminal domain. Here, the 2.5 Å resolution crystal structure of this 20‐amino‐acid peptide of AHNAK bound to the AnxA2–S100A10 heterotetramer (1:2:2 symmetry) is presented, which confirms the asymmetric arrangement first described by Rezvanpour and coworkers and explains why the binding motif has high affinity for (p11)2(AnxA2)2. Binding of AHNAK to the surface of (p11)2(AnxA2)2 is governed by several hydrophobic interactions between side chains of AHNAK and pockets on S100A10. The pockets are large enough to accommodate a variety of hydrophobic side chains, allowing the consensus sequence to be more general. Additionally, the various hydrogen bonds formed between the AHNAK peptide and (p11)2(AnxA2)2 most often involve backbone atoms of AHNAK; as a result, the side chains, particularly those that point away from S100A10/AnxA2 towards the solvent, are largely interchangeable. While the structure‐based consensus sequence allows interactions with various stretches of the AHNAK C‐terminal domain, comparison with other S100 structures reveals that the sequence has been optimized for binding to S100A10. This model adds new insight to the understanding of the specific interactions that occur in this membrane‐repair scaffold.

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The C Terminus of Annexin II Mediates Binding to F-actin

Cited by 114 publications

References 51 publications

Phosphoinositide Specificity of and Mechanism of Lipid Domain Formation by Annexin A2-p11 Heterotetramer

Phosphoinositide Specificity of and Mechanism of Lipid Domain Formation by Annexin A2-p11 Heterotetramer

Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2

Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

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