CoCoLysis : A Web-Accessible Coiled-Coil Protein Database with Analysis Tools

Coiled Coils are simple tertiary protein structures that are used frequently in studies involving protein folding and design. They are also one of the most common protein-protein interactions and it is estimated that 5-10% of the sequences revealed by genome projects encode coiled coil domains. There are currently several online databases of protein sequences; however, no database exists online specifically for coiled coil proteins. In this paper, we discuss a database specifically for coiled coil proteins, along with necessary application programs for stability and frequency analyses. Extracting the coiled coil proteins manually from the ExPASy or any other protein database is a tedious process. Also, new entries are added to the databases on a regular basis. We programmatically extract the protein sequences that contain coiled coils. The coiled coil parts of the protein sequences are also extracted. This data is loaded into a database that can be queried online. The information in the database can be updated to the latest additons by running an update script. The source of data for the database is Swiss-Prot and EMBL. Once source of data involves coiled coil domains that are obtained directly from these sites. The other source of data is the full protein sequence database at these same sites, but then we process them ourselves to find the coiled coil domains. ∗Department of Computer Science, University of Colorado, Colorado Springs, CO 80933 †Department of Computer Science, University of Colorado, Colorado Springs, CO 80933 ‡Department of Computer Science, University of Colorado, Colorado Springs, CO 80933 §Department of Biochemistry, University of Colorado Health Sciences Center, Denver, CO 80262 ¶Department of Biochemistry, University of Colorado Health Sciences Center, Denver, CO 80262 1 What are Coiled Coils A coiled coil is a tertiary oligomerization domain that is formed when two or more α-helices wrap around each other in a left-handed super coil. Coiled coils are found throughout nature and occur in a wide variety of proteins and play an important role in basic biology. Two examples are the kinesin [4] and myosin [5]. Kinesin is a molecule that transports cellular components from place to place. The ability to perform this is due in part to the coiled coil. Myosin, a fundamental protein used in muscle connections also employs coiled coil conformation to function properly [1]. Coiled coils are found to have hydrophobic amino acids spaced at every third and then every fourth residue within its sequence. A grouping of seven residues form a heptad repeat, designated abcdef where a and d positions are occupied by hydrophobic amino acids. This pattern repeats and on an average places a hydrophobic side chain every 3.5 residues per sequence. A typical α-helix has 3.6 residues per turn and takes less than two full heptads to turn twice. In a coiled coil, the two α-helices bury their hydrophobic residues in the center of the coil that causes the coiled coil itself to form a super coil. These are depicted in as positions a, a′, d and d′ in Figure 1. The super coil nature of the coiled coil also gives rise to interactions within the individual α-helices and between the α-helices in the super coil.