CC+: A Searchable Database of Validated Coiled coils in PDB Structures and AlphaFold2 Models

Abstract

ABSTRACTα-Helical coiled coils are common tertiary and quaternary elements of protein structure. In coiled coils, two or more α helices wrapped around each other to form bundles. This apparently simple structural motif can generate many architectures and topologies. Understanding the variety of and limits on coiled-coil assemblies and their sequence-to-structure relationships impacts on protein structure, design, and engineering. Coiled coil-forming sequences can be predicted from heptad repeats of hydrophobic and polar residues,hpphppp, although this is not always reliable. Alternatively, coiled-coil structures can be identified using the program SOCKET, which finds knobs-into-holes (KIH) packing between side chains of neighboring helices. SOCKET also classifies coiled-coil architecture and topology, thus allowing sequence-to-structure relationships to be garnered. In 2009, we used SOCKET to create a relational database of coiled-coil structures, CC+, from the RCSB Protein Data Bank (PDB). Here we report an update of CC+following the recent explosion of structural data and the success of AlphaFold2 in predicting protein structures from genome sequences. With the most-stringent SOCKET parameters, CC+contains ≈12,000 coiled-coil assemblies from experimentally determined structures, and ≈120,000 potential coiled-coil structures within single-chain models predicted by AlphaFold2 across 48 proteomes. CC+allows these and other less-stringently defined coiled coils to be searched at various levels of structure, sequence, and side-chain interactions. The identified coiled coils can be viewed directly from CC+using the Socket2 application, and their associated data can be downloaded for further analyses. CC+is available freely athttp://coiledcoils.chm.bris.ac.uk/CCPlus/Home.html. It will be regularly updated automatically.FOR THE BROADER AUDIENCEProtein assemblies and protein-protein interactions are key to all biological processes. α-Helical coiled coils are one of the most common modes of directing and stabilising these interfaces. Here, we report an updated CC+database of structurally validated coiled coils from experimental protein structures and AlphaFold2 models. CC+contains many thousands of coiled-coil structures and models, associated parameters, and sequences. It enables the compilation of rich datasets for advancing protein structure, design, and engineering research.