Protein cross-linking tools for the construction of nanomaterials

Across bioengineering there is a need to couple proteins to other proteins, or to peptides. Although traditional chemical conjugations have dominated in the past, more and more highly specific coupling strategies are becoming available that are based on protein engineering. Here we review the use of protein modification approaches such as enzymatic and autocatalytic protein-protein coupling, as well as the use of hetero-dimerizing (or hetero-oligomerizing) modules, applied to the specific case of linking together de novo designed recombinant polypeptides into precisely structured nanomaterials. Such polypeptides are increasingly being investigated for biomedical and other applications. In this review, we describe the protein-engineering based cross-linking strategies that dramatically expand the repertoire of possible molecular structures and, hence, the range of materials that can be produced from them.