Tania A. Baker
Massachusetts Institute of Technology
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Primary Section: 21, Biochemistry Membership Type:
Member
(elected 2007)
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Research Interests
All cells contain ATP-dependent protein unfoldases that function in protein-quality control and in many regulatory circuits. These protein machines promote ATP-dependent protein degradation and also disassemble stable protein complexes and aggregates. My recent work has focused on determining strategies of substrate recognition and the mechanism of protein unfolding used by the Clp/Hsp100 family of unfoldases, with major emphasis on the bacterial ClpX unfoldase. These studies reveal general principles that underlie both constitutive and regulated substrate recognition. Some substrates are recognized directly, generally via short sequence tags near the termini of the protein that serve as a binding handle for the enzyme. Other proteins are recognized in a regulated manner. Latent recognition tags can become accessible to the enzyme following protein cleavage, protein unfolding, or rearrangement of subunit interfaces. Adaptor proteins, which interact with both the unfoldase and the substrate, provide another mechanism for controlling substrate choice. We are currently studying the structure, function, and regulation of several different adaptor proteins and are investigating the mechanism of protein unfolding and how ATP hydrolysis is used to fuel the protein unfolding/translocation cycle.
