Crystal Structure of the Tetrameric Fibrinogen-like Recognition Domain of Fibrinogen C Domain Containing 1 (FIBCD1) Protein

Shrive, A.K.; Møeller, Jesper Bonnet; Burns, I.; Paterson, Janet M.; Shaw, Amy J.; Schlosser, Anders; Sørensen, Grith Lykke; Greenhough, Trevor J.; Holmskov, Uffe

doi:10.1074/jbc.m113.520577

Cited by 26 publications

(45 citation statements)

References 21 publications

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“…3), and crystal structures of the FBG domains of human ficolin-H, -L, and -M, angiopoietin-2, FIBCD-1, and crab thachylectin-5A exhibit the same subdomain organization and structural folds. [6][7][8][9][10] Human FRePs and wound healing A large body of literature reveals that FRePs play key roles during tissue repair. Each domain within these large multimodular molecules can interact with a wide variety of binding partners to mediate diverse effects on cell behavior.…”

Section: Discussion Definition Of Frepsmentioning

confidence: 99%

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

Zuliani-Alvarez

Midwood

2015

Advances in Wound Care

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Fibrinogen-related proteins (FRePs) comprise an intriguing collection of extracellular molecules, each containing a conserved fibrinogen-like globe (FBG). This group includes the eponymous fibrinogen as well as the tenascin, angiopoietin, and ficolin families. Many of these proteins are upregulated during tissue repair and exhibit diverse roles during wound healing. An increasing body of evidence highlights the specific expression of a number of FRePs following tissue injury and infection. Upon induction, each FReP uses its FBG domain to mediate quite distinct effects that contribute to different stages of tissue repair, such as driving coagulation, pathogen detection, inflammation, angiogenesis, and tissue remodeling. Despite a high degree of homology among FRePs, each contains unique sequences that enable their diversification of function. Comparative analysis of the structure and function of FRePs and precise mapping of regions that interact with a variety of ligands has started to reveal the underlying molecular mechanisms by which these proteins play very different roles using their common domain. Fibrinogen has long been used in the clinic as a synthetic matrix serving as a scaffold or a delivery system to aid tissue repair. Novel therapeutic strategies are now emerging that harness the use of other FRePs to improve wound healing outcomes. As we learn more about the underlying mechanisms by which each FReP contributes to the repair response, specific blockade, or indeed potentiation, of their function offers real potential to enable regulation of distinct processes during pathological wound healing.

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Section: Discussion Definition Of Frepsmentioning

confidence: 99%

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

Zuliani-Alvarez

Midwood

2015

Advances in Wound Care

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“…Phylogenetically, the FReDs of MFAP4 and FIBCD1 are closely related (48), and the homologous S1 ligand-binding site can be predicted within the FReD of MFAP4. (17). All of these residues were found to be important for FIBCD1 binding to acetylated structures, with slight binding impairment for Trp 443 mutant and total inhibition for the remaining three mutants (49).…”

Section: Discussionmentioning

confidence: 99%

“…The family includes several proteins engaged in tissue homeostasis and innate immunity, such as FIBCD1 (fibrinogen C domain-containing 1), ficolins, and angiopoietins (14 -16). The crystal structure of the FReD of several family members has been solved (17)(18)(19). The ligand-binding site, designated S1, is described in all the proteins and is located in close proximity to the calcium-binding site.…”

Section: Mfap4 (Microfibrillar-associated Protein 4)mentioning

confidence: 99%

Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin- and Fibrillin-binding Protein Involved in Elastic Fiber Formation

Pilecki

Holm

Schlosser

et al. 2016

Journal of Biological Chemistry

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116

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MFAP4 (microfibrillar-associated protein 4) is an extracellular glycoprotein found in elastic fibers without a clearly defined role in elastic fiber assembly. In the present study, we characterized molecular interactions between MFAP4 and elastic fiber components. We established that MFAP4 primarily assembles into trimeric and hexameric structures of homodimers. Binding analysis revealed that MFAP4 specifically binds tropoelastin and fibrillin-1 and -2, as well as the elastin cross-linking amino acid desmosine, and that it co-localizes with fibrillin-1-positive fibers in vivo. Site-directed mutagenesis disclosed residues Phe 241 and Ser 203 in MFAP4 as being crucial for type I collagen, elastin, and tropoelastin binding. Furthermore, we found that MFAP4 actively promotes tropoelastin self-assembly. In conclusion, our data identify MFAP4 as a new ligand of microfibrils and tropoelastin involved in proper elastic fiber organization.Elastic fibers are key extracellular matrix structural elements of connective tissues that undergo repeated stretch, such as large arteries and the lung (1). The fibers consist of two major components: an amorphous elastin core surrounded by a sheath of fibrillin-rich microfibrils (2). Elastin is a highly hydrophobic polymer of the soluble precursor tropoelastin (3). Tropoelastin is known to undergo a self-assembly process known as coacervation (4), often believed to be a first step in the process of elastic fiber maturation. Because of the high content of lysine residues within the tropoelastin sequence, its assembly into a polymeric form is stabilized by formation of desmosine crosslinks, catalyzed by the lysyl oxidase (LOX) 3 enzyme family (5).Microfibrils, the other major component of elastic fibers, provide the structural scaffold for the deposition of elastin globules. They consist primarily of fibrillin-1 and fibrillin-2, large glycoproteins with a high degree of homology (6). Apart from fibrillins, numerous accessory proteins have been shown to associate with microfibrils or elastin and promote formation of mature fibers, including fibulins and microfibril-associated glycoproteins (MAGPs) (7-10). The importance of proper elastogenesis has been underscored by gene deficiency studies: mice lacking elastin, LOX, or fibrillin-1 die shortly after birth because of vascular abnormalities (11-13).MFAP4 (microfibrillar-associated protein 4) is an extracellular matrix protein belonging to the fibrinogen-related domain (FReD) family. The family includes several proteins engaged in tissue homeostasis and innate immunity, such as FIBCD1 (fibrinogen C domain-containing 1), ficolins, and angiopoietins (14 -16). The crystal structure of the FReD of several family members has been solved (17-19). The ligand-binding site, designated S1, is described in all the proteins and is located in close proximity to the calcium-binding site. MFAP4 has been reported to form homodimeric structures that further oligomerize, but its definite oligomerization pattern has not been established (20).MFAP4 is conside...

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“…One receptor of chitin is FlCBD1, which is an endocytic, membrane protein that binds the acetyl group of chitin through a extracellular, fibrinogen-like, recognition domain. It is expressed on enterocytes of the gut and on airway and salivary epithelial cells (63). Other proteins that bind chitin are secreted.…”

Section: Chitin and Chitosanmentioning

confidence: 99%

Exploiting fungal cell wall components in vaccines

et al. 2014

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Innate recognition of fungi leads to strong adaptive immunity. Investigators are trying to exploit this observation in vaccine development by combining antigens with evolutionarily conserved fungal cell wall carbohydrates to induce protective responses. Best studied is β-1,3-glucan, a glycan that activates complement and is recognized by Dectin-1. Administration of antigens in association with β-1,3-glucan, either by direct conjugation or complexed in glucan particles, results in robust humoral and cellular immune responses. While the host has a host of mannose receptors, responses to fungal mannoproteins generally are amplified if cells are cooperatively stimulated with an additional danger signal such as a toll-like receptor agonist. Chitosan, a polycationic homopolymer of glucosamine manufactured by the deacetylation of chitin, is being studied as an adjuvant in DNA and protein-based vaccines. It appears particularly promising in mucosal vaccines. Finally, universal and organism-specific fungal vaccines have been formulated by conjugating fungal cell wall glycans to carrier proteins. A major challenge will be to advance these experimental findings so that at risk patients can be protected.

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Crystal Structure of the Tetrameric Fibrinogen-like Recognition Domain of Fibrinogen C Domain Containing 1 (FIBCD1) Protein

Cited by 26 publications

References 21 publications

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin- and Fibrillin-binding Protein Involved in Elastic Fiber Formation

Exploiting fungal cell wall components in vaccines

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