Applications of Chemical Cross-Linking to the Study of Biological Macromolecules
Elucidation of the location of intra-and interchain chemical cross-links in proteins has helped unravel the folding process of polypeptide chains. The most common naturally occurring inter-and intramolecular linkage is the disulŠde bond. Other examples include transglutaminase-catalyzed formation of amide bonds between γ-carboximide groups of glutamines and the ε-amino groups of lysines in Šbrin1 and the extremely complex cross-linking in collagen.2,3 Determination of the locations of these cross-linkages has contributed to our understanding of the tertiary and quaternary structures of proteins. It follows, therefore, that the introduction of stable covalent linkages between amino acid residues in the native states of proteins should provide additional means for the study of interresidue distances, the relationship between various protein domains, the conformational states of a protein and the interactions of polypeptide chains in solution.