STRUCTURAL STUDIES OF THE 70 KDA SECB CHAPERONE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SecB is a bacterial molecular chaperone that is a critical component of the Sec secretion system. It is not only responsible for recognizing and maintaining preproteins in an extended, secretion-competent state and delivering them to the export apparatus at the peripheral membrane, but may also function as a general cytosolic chaperone. SecB binds a vast array of unfolded protein sequences in vitro, yet is highly selective in vivo. The structural and energetic mechanisms behind recognition are poorly understood, but it is believed SecB uses multiple binding subsites with different chemical properties to promote a specificity to diverse substrates. As functional homologs are found in all forms of life, SecB serves as an amenable system with which to explore in detail the recognition and binding processes involved. The objective of this proposal is to structurally characterize SecB in complex with representative peptide substrates and to define the dynamic, mechanistic and thermodynamic parameters underlying SecB-ligand recognition and binding specificity.