Zinc finger structure determination by NMR: Why zinc fingers can be a handful

Zinc fingers can be loosely defined as protein domains containing one or more tetrahedrally-co-ordinated zinc ions whose role is to stabilise the structure rather than to be involved in enzymatic chemistry; such zinc ions are often referred to as structural zincs. Although structural zincs can occur in proteins of any size, they assume particular significance for very small protein domains, where they are often essential for maintaining a folded state. Such small structures, that sometimes have only marginal stability, can present particular difficulties in terms of sample preparation, handling and structure determination, and early on they gained a reputation for being resistant to crystallisation. As a result, NMR has played a more prominent role in structural studies of zinc finger proteins than it has for many other types of pro-teins. This review will present an overview of the particular issues that arise for structure determination of zinc fingers by NMR, and ways in which these may be addressed. (c) 2022 MRC Laboratory of Molecular Biology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

Zinc fingers are protein domains containing one or more tetrahedrally co-ordinated zinc ions that stabilize the structure. They are particularly important for small protein domains to maintain a folded state. Due to difficulties in crystallization, NMR has played a more prominent role in studying zinc finger proteins.