Modular Construction of Knot Matrix Proteins

It is now apparent that proteins in this class are constructed by combining substructures. Evolution has a family of knots to use in new experiments and also a broader and more variable family of matrices. The elementary unit is the functional domain defined in a broad way by its knot and in a most specific way by its matrix and surface. Much of evolution consists of experiments in which matrix and surface modifications are tested for acceptance or rejection, but the experiments are roughly of two kinds. In one, new knots are found and thus potentially new functions. In the other, new functions are found by combining old functional domains and tailoring matrices and surfaces for the new function. A variety of combinations of knots and matrices are possible and all seem to have known representatives. All-knot proteins are of the structural class, almost perfect H-bonded secondary structure (e.g., keratins). Semiknot proteins have generally low B factors but variable knot-forming abilities. The knot regions are not fixed in the sequence order but vary in position and size with functional state. The immunoglobulins are discussed in Sec. VI.F as probable examples of this type. Knot-matrix proteins have knots and matrices in almost any proportion and the knots are fixed in sequence position. For high thermal stability with retention of physiological function, knots must be either large or exceptionally stable or both. Enzymes have two knots per catalytic function but may also have structural knots such as hinge knots to strengthen and establish the association of the functional domains. When the two functional domains are on different proteins, they are usually held together to form the catalytic unit by knots formed from parts of both proteins. Many proteins consist of a single functional domain, e.g., most proteinase inhibitors. By current tests and with current data the hemoglobins have no knots. Proteins like the serum albumins and insulin have not yet been examined for their classification.

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