Domains fibronectin

In the extracellular region, cytokine receptors have characteristic sequence sections that specify the particular receptor type. Cys-rich domains, fibronectin type Ill-like domains and immimoglobulin-like domains can be differentiated. Cytokine receptors of type I often have a conserved WSXWS motif in the extracellular region. 

Figure 1 Schematics of the domain structures of the MMP family. The catalytic domain (represented by light purple) has an insertion of gelatin binding domain (fibronectin type-ll-like domain) in MMP-2 and MMP-9. In all other MMPs, the catalytic domain is a continuous entity. Transmembrane and cytoplasmic regions (represented by yellow) are found in membrane-bound MMPs only.

In the extracellular region, cytokine receptors have characteristic sequence sections that specify the particular receptor type. Cys-rich domains, fibronectin-type IH-like domains and immunoglobulin-like domains can be differentiated, among others. Cytokine receptors of type I often have a conserved WSXWS motif in the extracellular region. With the exception of ciliary neurotrophic receptor, which is membrane-anchored via a GPI anchor (see Section 3.7.4), all receptors have a single transmembrane domain of 22 - 28 amino acids. Two motifs, called box 1 and box 2, are relatively conserved in the membrane-proximal part of the cytoplasmic domain. However, no known catalytic domain is found on the cytoplasmic part of the receptors. 

Fig. 8. Structures of LI, MAG and PO glycoproteins. The sequences of LI (a), MAG (b) and PO (c) glycoproteins predicted from analysis of cDNA clones as well as protein in the case of PO are shown to variably include in the extracellular portions Ig-like domains, fibronectin type III repeats (hatched), a transmembrane segment and a cytoplasmic domain. Potential A-glycosylation sites are indicated (open circle). Splicing variants in the cytoplasmic domains of LI and MAG are shown (open triangle).

Figure 13.19 Ribbon diagram of the stmcture of the extracellular domain of the human growth hormone. The hormone-binding region is formed by loops (yellow) at the hinge region between two fibronectin type III domains. (Adapted from J. Wells et al., Annu. Rev.

Figure 15.24 Ribbon diagram (a) and topology diagram (b) of the fibronectin type III domain, which is composed of a three-stranded and a four-stranded p sheet packed together as a compressed barrel.

Leahy, D.J., Hendrickson, W.A., Aukhil, A., Erickson, H.P. 5tructure of a fibronectin type II domain from tenascin phased by MAD analysis of the selenome-thionyl protein. Science 258 987-991, 1992. 

C, which is found in complement proteins FI, F2, and F3, first found in fibronectin I, the immunoglobulin superfamily domain N, found in some growth factor receptors E, a module homologous to the calcium-binding E-F hand domain and LB, a lectin module found in some cell surface proteins. (Adapted from Baron, M., Norman, D., and Campbell, I., 1991, Protein modnles. Trends in Biochemical Sciences 16 13—1 7.)... 

The leukocyte integrin a 4(3 1 (also known as VLA-4 and CD49d/CD29) is a cell adhesion receptor, which is predominantly expressed on lymphocytes, monocytes and eosinophils. VLA-4 is generally selective for the CS1 domain within fibronectin, with an essential requirement for LDV sequence for binding. VLA-4 also binds to VCAM-1 as a counter receptor. 

The integrin a 4(3 7 is restricted to leukocytes and can bind not only to VCAM1 and fibronectin, but also to MAdCAM the mucosal addressin or homing receptor, which contains immunoglobulin-like domains related to VCAM-1. 

Kim J. Han L Kim Y. et al. C-terminal heparin-binding domain of fibronectin regulates integrin-mediated cell spreading but not the activation of mitogen-activated protein kinase / / Biochem. J. 2001. V. 360. P. 239-245. 

Figure 48-3. Schematic representation of fibronectin. Seven functional domains of fibronectin are represented two different types of domain for heparin, cell-binding, and fibrin are shown. The domains are composed of various combinations of three structural motifs (I, II, and III), not depicted in the figure. Also not shown is the fact that fibronectin is a dimer joined by disulfide bridges near the carboxyl terminals of the monomers. The approximate location of the RGD sequence of fibronectin, which interacts with a variety of fibronectin integrin receptors on cell surfaces, is indicated by the arrow. (Redrawn after Yamada KM Adhesive recognition sequences.

Fig. 2). Not all MMPs have these domains, for example, matrilysin lacks the C-terminal domain and the MT-MMPs do not have the propeptide. Some MMPs have additional domains, for example, the gelatinases have three repeats of a fibronectin-type II domain. 

Members of this family of molecules may have only one Ig-like domain, as is the case for the myelin protein P0, or, as for most of the family, have many Ig domains. In addition to the subclassification of Ig domains into V-, C- and C2-like domains, Ig family members can be broadly divided into three general classes [8] (a) those that have only Ig-like domains (b) those that have Ig domains and additional domains that resemble regions of the ECM component fibronectin, termed FN-like domains and (c) those that have Ig domains and motifs other than FN-like domains. Moreover, any one Ig family member may have many isoforms, which may differ in the length of the cytoplasmic domain, in their post-translational modifications and whether they are membrane-spanning or glycosylphos-phatidylinositol (GPI)-anchored proteins (see Box 3-1). Also, additional amino acid sequences inserted in the extracellular domain may distinguish isoforms of a particular IgCAM. While it is not known how the majority... 

FIGURE 7-1 The immunoglobulin (Ig) gene family of molecules. Several varieties of Ig domain-containing molecules are contained within the Ig gene superfamily. Most are type I membrane proteins some have only Ig domains or other moieties that may convey function (see text). V, variable Ig domain C, constant Ig domain MAG, myelin-associated glycoprotein NCAM, neural cell adhesion molecule GPI, glycosylphosphatidyl-inositol EC, extracellular domain FN, fibronectin. 

FIGURE 7-3 Integrins are heterodimers. Integrins consist of a and 3 subunits noncovalently linked, which interact via their cytoplasmic domains with a number of cytoplasmic proteins. The axpi integrin complex on the left binds to a complex which includes focal adhesion kinase (FAK). The a6P4 integrin complex contains fibronectin (FN) III repeats, which mediate binding to intermediate filaments. 

Brummendorf, T. and Rathjen, F. G. Axonal glycoproteins with immunoglobulin and fibronectin type II-related domains in vertebrates Structural features, binding activities and signal transduction. /. Neurochem. 61 1207-1219, 1993. 

The extracellular domain of RPTKs can be composed of different structural motifs. For instance, the EGFR extracellular domain contains two cysteine-rich regions. The PDGFR extracellular domain consists of five immuno-globulin-like repeats. Other domains found in the extracellular region of RPTKs include fibronectin III repeats,... 

The carboxy-terminal region in apolipoprotein (a) closely resembles the protease domain in plasminogen [eight amino acid substitutions, nine amino acid deletions, and one insertion in apo(a) relative to plasminogen, with 94% overall nucleotide sequence identity] (G28). The most important difference is the substitution of arginine by serine in the site responsible for proteolytic activity (position 4308) (G28). As a result, Lp(a) has no protease activity towards substrates for plasmin (J3). Salonen (SI) reported a serine-protease activity of Lp(a) towards fibronectin, a glycoprotein present in connective tissue matrices. 

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