Serine protease

I/C7 repeat

Figure 3 The modular structure of C1r, C1s, C2 and factor I. MASP-1 and MASP-2 have the same modules as C1r and C1s. (This diagram is adapted from the work of Dr A. J. Day.)

tains an EGF (epidermal growth factor) module, which is the Ca2~-binding site. Each also contains two internal repeats of about 100 amino acids, known as CUB (Clr/Cls, Uefg, Bmpl) modules, and two CCP (complement control protein) modules, each about 60 amino acids long. CCP molecules are found in many complement proteins, and are a particular feature of the proteins which interact with C3 and C4 turnover, such as factor H, C4bp, CR1, MCP and DAF. The CUB domains are likely to be involved in binding to Clq.

The overall structure of each Clr or Cls monomer is a dumb-bell shape, with two globular regions of unequal size connected by a short strand. Isolated Clr exists as an elongated dimer, with the dumbbells joined end to-end. Two molecules of Cls bind, one to each end of the Clr dimer, in the presence of Ca24 ions. This forms the very elongated Clr2Cls2 tetramer, which binds to the collagenous regions of Clq. The structure of the large CI complex is not clearly established, but several models which indicate how Clr2Cls2 might interact with Clq have been proposed (see Colomb et al, 1989 for review).

Activation of CI occurs when two or more globular heads of Clq bind to a complement activator: movement of the heads is transmitted by the collagenous stalks to the core region and thence to Clr. A conformational change is induced in Clr, which causes the Clr molecules to cleave and activate each other: these then cleave and activate the Cls molecules. During this process, each Clr and Cls monomer is cleaved at the N-terminal end of the serine protease domain, forming a structure with two disul-fide-linked polypeptide chains of approximately 56 and 28 kDa. The activated forms have very restricted proteolytic activity: activated Clr will cleave only proenzymic Cls, and activated Cls will cleave only C2 and C4. Both proteases have arginyl specificity. Both also have a low level of esterase activity towards esters of basic (Clr) or basic and hydrophobic (Cls) amino acids. In older literature, activated Cls is often described as CI esterase, and the nomenclature Clr, Cls, and occasionally CTr, CTs denoting the activated forms, is also frequently encountered.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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