Karl W. Volz
PhD, University of California, San Diego
Room: 1110 MBRB, Tel: 312-996-2314
Structural Analysis of Cellular Regulatory Proteins
My laboratory uses the tools of protein crystallography and molecular biology to analyze the structural determinants of protein function in a variety of cellular regulatory processes.
Our current research project focuses on the structure and function of iron regulatory protein-1 (IRP1) in its dual roles as a [4Fe-4S] cluster-containing cytosolic aconitase or an mRNA-binding regulatory protein. We elucidated the interconversion mechanism of IRP1 from aconitase to mRNA repressor by solving the first crystal structure of an IRP1:RNA complex.
Recent projects concerned unique members of the serine-protease-inhibitor (serpin) superfamily. We solved the structures of the anti-apoptotic viral serpin crmA, the anti-tumor serpin maspin, and the anti-angiogenic factor PEDF to reveal the non-standard functionalities of these important serpin homologues.
Results from our YjgF project presaged the problem of structure-based functional assignment in structural genomics. Our 1.2 Å structure of E. coli YjgF was the first for any member of the ubiquitous YjgF protein family. Oddly, seven structures later, the functions of the YjgF family members are still unknown.
Early projects concentrated on CheY, a phosphorylatable protein that regulates bacterial chemotaxis. We determined the structures of apo CheY, activating and inactivating CheY mutants, covalently activated CheY, and CheY in a meta-active state. These functional insights were directly applicable to the hundreds of response regulators in bacterial two-component systems.