Anastellin, an FN3 Fragment with Fibronectin Polymerization Activity, Resembles Amyloid Fibril Precursors

Briknarová, Klára; Åkerman, Maria E.; Hoyt, David; Ruoslahti, Erkki; Ely, Kathryn R.

doi:10.1016/s0022-2836(03)00890-8

Cited by 72 publications

(99 citation statements)

References 61 publications

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“…1B,C), in agreement with previously published images of such artificial Fn fibers (Ejim et al, 1993;Wojciak-Stothard et al, 1997). Indeed, cryo-scanning electron microscopic images suggest that Fn fibers exist as 'cables' comprised of individual fibrous strands of ~5-15 nm in diameter and larger (Chen et al, 1978;Dzamba and Peters, 1991;Peters et al, 1998;Singer, 1979) which are proposed to be held together by hydrogen bonds, intermolecular beta-strand swapping (Briknarova et al, 2003;Litvinovich et al, 1998), disulfide bonds which are potentially formed by cryptic disulfide isomerase activity (Langenbach and Sottile, 1999), and other weak electrostatic interactions (Chen and Mosher, 1996;Morla et al, 1994). Although the exact location and properties of these bonds are unknown, it has been observed that they are strong enough to render cell-derived Fn fibers irreversibly insoluble in 1% de-oxycholate (McKeown-Longo and Mosher, 1983), which is a phenomenon we observed with manually deposited Fn fibers as well (data not shown).…”

Section: Manually Deposited Fn Fibers Bundle Into Fiber Cables Similasupporting

confidence: 89%

Assay to mechanically tune and optically probe fibrillar fibronectin conformations from fully relaxed to breakage

et al. 2008

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In response to growing needs for quantitative biochemical and cellular assays that address whether the extracellular matrix (ECM) acts as a mechanochemical signal converter to co-regulate cellular mechanotransduction processes, a new assay is presented where plasma fibronectin fibers are manually deposited onto elastic sheets, while force-induced changes in protein conformation are monitored by fluorescence resonance energy transfer (FRET). Fully relaxed assay fibers can be stretched at least 5-6 fold, which involves Fn domain unfolding, before the fibers break. In native fibroblast ECM, this full range of stretch-regulated conformations coexists in every field of view confirming that the assay fibers are physiologically relevant model systems. Since alterations of protein function will directly correlate with their extension in response to force, the FRET vs. strain curves presented herein enable the mapping of fibronectin strain distributions in 2D and 3D cell cultures with high spatial resolution. Finally, cryptic sites for fibronectin's N-terminal 70-kD fragment were found to be exposed at relatively low strain, demonstrating the assay's potential to analyze stretch-regulated protein-rotein interactions.

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Section: Manually Deposited Fn Fibers Bundle Into Fiber Cables Similasupporting

confidence: 89%

Assay to mechanically tune and optically probe fibrillar fibronectin conformations from fully relaxed to breakage

et al. 2008

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“…However, there are several approaches to make artificial FN aggregates that resemble the matrix. One of the methods uses anastellin, a truncated form of the first FNIII domain, lacking the A and B ␤ strands (35,36). Anastellin binds FN to form a large aggregate, called superFN, which has FN matrix-like fibrillar structures when observed by light microscopy.…”

Section: Fibronectin (Fn)mentioning

confidence: 99%

Fibronectin Aggregation and Assembly

Ohashi

Erickson

2011

Journal of Biological Chemistry

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The mechanism of fibronectin (FN) assembly and the selfassociation sites are still unclear and contradictory, although the N-terminal 70-kDa region ( I 1-9) is commonly accepted as one of the assembly sites. We previously found that I 1-9 binds to superfibronectin, which is an artificial FN aggregate induced by anastellin. In the present study, we found that I 1-9 bound to the aggregate formed by anastellin and a small FN Fibronectin (FN)2 is a secreted protein expressed in the liver and circulated in blood as a soluble dimer (1). In addition to this plasma FN, some cell types, such as fibroblasts and endothelial cells, secrete FN and assemble it into extracellular matrix fibrils. FN is a modular protein containing 12 FN type I (FNI) domains, two FN type II domains, and 15-17 FN type III (FNIII) domains (2, 3). Two cysteines at the C terminus asymmetrically form interchain disulfide bonds (4, 5). Dimeric FN molecules interact with each other on the cell surface to form matrix fibrils. This process requires cell surface integrins (6 -9). Live cell imaging showed that integrin translocation by the actin cytoskeleton is crucial for the early stages of FN matrix assembly (10, 11). More recently, it has been reported that cell-to-cell adhesion via cadherin controls tissue tension and affects FN matrix formation during embryogenesis (12).The FN matrix had long been thought to be formed by disulfide-bonded FN multimers because the protein migrated at the top of an SDS gel under nonreducing conditions (13-16). However, studies by Chen and Mosher (17) A recent NMR study showed a unique structure for the domain pair III 1-2 (32). It had been recognized from sequence analysis that there is an 18-amino acid linker between these domains. The NMR structure showed that the A strand of III 2 was disordered, giving a total length of ϳ35 amino acids for the linker, and further indicated that III 1 and III 2 formed a closed compact structure, with a potential salt bridge between Lys-669 in III 1 and Asp-767 in III 2. These two amino acids were mutated to alanine, giving the mutant designated KADA. The native III 1-2 was found not to bind I 1-5, but the KADA mutation was reported to dramatically enhance binding of I 1-5, as measured by surface plasmon resonance.

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“…Third, CP1 and anastellin are complementary structural counterparts in homologous FNIII structures. Anastellin is a N-terminal deletion fragment of 1FNIII lacking the N terminus that includes strands A and B (45), which is the region spanning CP1 in 10FNIII. Despite differences in ␤ strand coverage of the FNIII structure, both systems display hydrophobic surfaces to solvent.…”

Section: Discussionmentioning

confidence: 99%

“…Despite differences in ␤ strand coverage of the FNIII structure, both systems display hydrophobic surfaces to solvent. The multimerization sequence is unstructured and exposes hydrophobic binding surfaces upon interaction with 10FNIII, whereas anastellin possesses exposed hydrophobic binding pockets for ANS in its residual structure (37,45).…”

Section: Discussionmentioning

confidence: 99%

“…FN assembly, in the context of superfibronectin and 9FNIII multimer formation, has been hypothesized to follow a process of intermolecular ␤-strand exchange, where ␤-strands from one partially unfolded domain complements a similarly unfolded intermediate of another domain to form a stable polymeric structure (38,40,45). FN assembly initiated by other peptide sequences in addition to anastellin, including peptides anginex, CLT1, and BBK32, has also been described to follow a ␤-structure-mediated process (50 -52).…”

Section: Discussionmentioning

confidence: 99%

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SLLISWD Sequence in the 10FNIII Domain Initiates Fibronectin Fibrillogenesis

Gee

Yüksel

Stultz

et al. 2013

Journal of Biological Chemistry

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Background: Fibronectin matrix assembly is mediated by cell traction at the RGD loop of 10FNIII, which is predicted to unravel ␤-strands A and B. Results: Sequence SLLISWD from strand B initiates fibronectin multimerization. Conclusion: SLLISWD mediates cell-mediated fibronectin fibril assembly. Significance: This matrix motif provides insight into physiological fibronectin fibrillogenesis with utility in initiating matrix assembly for tissue repair.

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Anastellin, an FN3 Fragment with Fibronectin Polymerization Activity, Resembles Amyloid Fibril Precursors

Cited by 72 publications

References 61 publications

Assay to mechanically tune and optically probe fibrillar fibronectin conformations from fully relaxed to breakage

Assay to mechanically tune and optically probe fibrillar fibronectin conformations from fully relaxed to breakage

Fibronectin Aggregation and Assembly

SLLISWD Sequence in the 10FNIII Domain Initiates Fibronectin Fibrillogenesis

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