The first EGF-like domain from human factor IX contains a high-affinity calcium binding site.

Handford, Penny A.; Baron, Martín; Mayhew, Mark; Willis, Anthony C.; Beesley, T; Brownlee, George G.; Campbell, Iain D.

doi:10.1002/j.1460-2075.1990.tb08133.x

Cited by 186 publications

(109 citation statements)

References 32 publications

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“…It is unknown whether the protein-protein interaction actually occurs inside or outside of the nucleus (33). Consequently, it is possible that the initial interaction does not take place in the nuclear environment, and yeast have been shown to be quite favorable to folding and disulfide bond formation in recombinant proteins and domains (34). However, although secondary and tertiary structure frequently contribute to protein recognition and subsequent interaction, the basis for protein-protein interaction can also be embedded in the linear amino acid sequence of the interacting domains.…”

Section: Discussionmentioning

confidence: 99%

Type VI Collagen Anchors Endothelial Basement Membranes by Interacting with Type IV Collagen

Kuo

Maslen

Keene

et al. 1997

Journal of Biological Chemistry

299

215

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Type VI collagen filaments are found associated with interstitial collagen fibers, around cells, and in contact with endothelial basement membranes. To identify type VI collagen binding proteins, the amino-terminal domains of the ␣1(VI) and ␣2(VI) chains and a part of the carboxyl-terminal domain of the ␣3(VI) chain were used as bait in a yeast two-hybrid system to screen a human placenta library. Eight persistently positive clones were identified, two coding the known matrix proteins fibronectin and basement membrane type IV collagen and the rest coding new proteins. The amino-terminal domain of ␣1(VI) was shown to interact with the carboxylterminal globular domain of type IV collagen. The specificity of this interaction was further studied using the yeast two-hybrid system in a one-on-one format and confirmed by using isolated protein domains in immunoprecipitation, affinity blots, and enzyme-linked immunosorbent assay-based binding studies. Co-distribution of type VI and type IV collagens in human muscle was demonstrated using double labeling immunofluorescent microscopy and immunoelectron microscopy. The strong interaction of type VI collagen filaments with basement membrane collagen provided a possible molecular pathogenesis for the heritable disorder Bethlem myopathy.Type VI collagen filaments are ubiquitous. They are present in all connective tissues that contain type I and type III collagen fibers and in cartilage, a tissue that contains predominantly type II collagen. The major functions that have been suggested for type VI collagen filamentous networks are as a substrate for cell attachment and as an anchoring meshwork that connects collagen fibers, nerves, and blood vessels to the surrounding matrix (1, 2). This implies that not only is there an interaction, either direct or indirect, with the type I/III collagen fibers but also that there is an interaction with components of endothelial basement membranes.Matrix components that have been shown to interact with type VI collagen in vitro include proteoglycans, collagens, hyaluronan, heparin, and integrins.Proteoglycans appear to be particularly important, since cell surface-, basement membrane-, and collagen fibril-associated proteoglycans have all been reported to bind to various forms of type VI collagen. Decorin is a small dermatan sulfate proteoglycan that binds to fibrillar collagens (3). It was shown that the leucine-rich module of the core protein bound to type VI and that the binding could be inhibited by the core proteins of fibromodulin and biglycan (4). The cell surface-associated membrane chondroitin sulfate proteoglycan NG2 was originally detected in cells from the rodent central nervous system but subsequently was also detected in blood vessels and cartilaginous structures of the head, neck, and spine. It interacts via its core protein with type VI collagen and is thought to provide machinery for transmembrane signaling (5). Since ␣1␤1 and ␣2␤1 integrins also bind type VI collagen (6, 7), the cell signaling potential of this molecule woul...

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Section: Discussionmentioning

confidence: 99%

Type VI Collagen Anchors Endothelial Basement Membranes by Interacting with Type IV Collagen

Kuo

Maslen

Keene

et al. 1997

Journal of Biological Chemistry

299

215

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“…Since the binding region identified so far consists of some 150 -180 amino acid residues, the recombinant production of this structure and of several shorter variants seems the better choice. This is feasible based on cDNA clones described for several laminin B2 chains [14,26,271; recombinant methods were recently used for the production of a single, calcium-binding EGF-like repeat from coagulation factor IX [30]. We have recently prepared a recombinant 300-residue C-terminal fragment of nidogen in mammalian cells [31] which, as predicted from fragment studies [ll], binds strongly to laminin P1.…”

Section: Discussionmentioning

confidence: 99%

Localization of a major nidogen‐binding site to domain III of laminin B2 chain

Gerl

Mann

Aumailley

et al. 1991

European Journal of Biochemistry

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The large pepsin fragments PI and PlX, which comprise most of the rod-like domains 111 of the three short arms of laminin from the mouse Engelbreth-Holm-Swarm tumor, possess full binding activity for nidogen in radioligand assays. Partial reduction (70-80%) of disulfide bonds in PI did not reduce binding activity and allowed the separation of domain 111 segments originating from the A, B1 and B2 chains of laminin as demonstrated by sequence analysis. Only the B2 chain segment consisting of seven cysteine-rich repeats with similarity to epidermal growth factor showed substantial nidogen-binding activity. Further degradation of this component to an active 28-kDa fragment was achieved by a second pepsin digestion of partially reduced P1. This indicates that a major binding structure for nidogen is located within three or four cysteine-rich repeats occupying sequence positions 755 to about 920 in the B2 chain. The data also show that fragments P1 and PIX differ by the absence or presence of a large portion, domain IIIb, of the laminin A chain but are indistinguishable in nidogen binding.A noncovalent complex of the basement membrane proteins laminin and nidogen (entactin) can be obtained in high yields from the mouse Engelbreth-Holm-Swarm (EHS) tumor using chelating agents in the extraction buffer [I]. Such complexes may represent an abundant structure in various basement membranes as indicated by immunological studies of cell cultures and tissue extracts [2 -41. The physiological and structural consequences of the formation of the complex are not fully understood. Since nidogen has the potential to bind cells by an Arg-Gly-Asp (RGD) sequence [5, 61 and to interact with calcium [6] and collagen type IV [7], properties also shared by laminin [8 -101, the complex between both proteins may be a more versatile structure in forming matrix contacts and mediating cell -matrix interactions.Chemical and immunological analyses of the lamininnidogen complex and its visualization by rotary shadowing demonstrated a 1 :1 molar ratio between both components (each about 50-60 amino acids) originating from A, B1 and B2 chains. Digestion of the laminin-nidogen complex by elastase produced similar fragments, such as ElXNd, which were larger than P1 and composed of laminin and nidogen fragments requiring dissociation with 2 M guanidine . HCl for their separation [l 11. Sensitive radioligand assays between both interacting partners demonstrated that the minimal association constant of the laminin-nidogen complex is of the order of 10* M. The laminin fragment P1 structure also contains a cryptic, RGD-dependent cell-binding site likely to be derived from the A chain segment [8] and the corresponding cellular receptors have a similarly high association constant 1161.In the present study we have approached the localization of nidogen-binding sites within EHS tumor laminin fragment P1 in order to provide a more advanced structural basis for studying biological implications of the complex formation. Because of the high extent of disulfide b...

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“…CUB domains are thought to mediate protein-protein interactions (Bork and Beckmann, 1993). EGF-like domains bind Ca 2+ in some proteins (Handford et al, 1990), but the Ca 2+ -dependent proteolytic activites of BMP1/TLD-like proteinases do not appear to rely on Ca 2+ binding to EGF motifs (Garrigue-Antar et al, 2004;. Rather, EGF domains bound to Ca 2+ may confer a rigid configuration to portions of BMP1/TLD-like proteinase, thereby affecting their structural and functional properties.…”

Section: Bmp1/tld Family Membersmentioning

confidence: 99%

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

2007

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A decade ago, bone morphogenetic protein 1 (BMP1) was shown to provide the activity necessary for proteolytic removal of the C-propeptides of procollagens I-III: precursors of the major fibrillar collagens. Subsequent studies have shown BMP1 to be the prototype of a small group of extracellular metalloproteinases that play manifold roles in regulating formation of the extracellular matrix (ECM). Soon after initial cloning of BMP1, genetic studies showed the related Drosophila proteinase Tolloid (TLD) to be necessary for formation of the dorsal-ventral axis in early embryogenesis. It is now clear that the BMP1/TLD-like proteinases, conserved in species ranging from Drosophila to humans, act in dorsal-ventral patterning via activation of transforming growth factor β (TGFβ)-like proteins BMP2, BMP4 (vertebrates) and decapentaplegic (arthropods). More recently, it has become apparent that the BMP1/TLD-like proteinases are key activators of a broader subset of the TGFβ superfamily of proteins, with implications that these proteinases may be key in orchestrating formation of ECM with growth factor activation and BMP signaling in morphogenetic processes.

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The first EGF-like domain from human factor IX contains a high-affinity calcium binding site.

Cited by 186 publications

References 32 publications

Type VI Collagen Anchors Endothelial Basement Membranes by Interacting with Type IV Collagen

Type VI Collagen Anchors Endothelial Basement Membranes by Interacting with Type IV Collagen

Localization of a major nidogen‐binding site to domain III of laminin B2 chain

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

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