Intracellular protein degradation is a major post-translational regulatory mechanism and plays a crucial role in many vital cellular functions; it also serves to remove damaged, denatured, and other abnormal proteins. In collaboration with Dr. Maurizi at LCB, my group has determined the crystal structure of the full-length ClpA, the regulatory component of the ClpAP complex. As the first crystal structure of AAA+ protein to be determined with two AAA+ modules, the ClpA structure has provided insights into the structural basis for the functional difference of the two AAA+ modules. My group has also obtained the structure of the isolated N-domain of ClpA in complex with ClpS that is known to alter the substrate selectivity in ClpA, much like the adaptor proteins used by many other AAA+ proteins (Maurizi and Xia, 2004). We also defined the function of the ClpA N-terminal domain by analyzing crystallographically details of its multiple protein and peptide binding sites (Xia et al., 2004). Having obtained structures of all components in the ClpAPS system, our group is now focusing on obtaining structures of ClpA in various conformations induced by bound nucleotides, and on crystallizing binary complexes of ClpA with either ClpS or ClpP, as well as with various substrates.
| Maurizi, Michael R; Xia, Di (2004) Protein binding and disruption by Clp/Hsp100 chaperones. Structure 12:175-83 |
| Xia, Di; Esser, Lothar; Singh, Satyendra K et al. (2004) Crystallographic investigation of peptide binding sites in the N-domain of the ClpA chaperone. J Struct Biol 146:166-79 |
