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Date Submitted

Spring 4-17-2015

Research Mentor and Department

Petra Anne Levin




The bacterial tubulin homologue FtsZ polymerizes in vitro in a GTP-dependent manner to form long, single stranded filaments. In cells, these filaments assemble at the nascent division site, interacting laterally to form the contractile Z-ring, which serves as a scaffold for the rest of the division machinery and constricts at the leading edge of the invaginating septum during cytokinesis. FtsZ consists of three primary domains: the N-terminal globular core consisting of 315 residues that contains the GTP-binding site, a variable and flexible C-terminal linker (CTL) consisting of 50 residues, and a conserved region at the C-terminus consisting of 17 residues known as the grappling-hook peptide (GHP) containing binding sites for modulatory proteins. The CTL was recently shown to behave as a flexible intrinsically disordered peptide (IDP) that is required for FtsZ assembly in vitro and function in vivo. To gain insight into the role of the CTL in FtsZ assembly, I am testing the structural parameters that define a functional CTL. Using computational predictions developed by the Pappu lab, we have generated six CTL variants in the context of native FtsZ: CTLV1-CTLV6. By changing the order and patterning of charged residues in the IDP sequence, these variants undertake conformations ranging from linear to globular or hairpin-like structures. To characterize the impact of these variants on Z-ring formation in vivo, I am assessing their impact on Z-ring formation, growth, and division in the model bacterium Bacillus subtilis. My results suggest a range of CTL conformations is tolerated, but extremely flexible or rigid linkers can lead to instability and aberrant FtsZ assembly in vivo. Experiments performed with synthetic CTL linkers yield results that support this conclusion.

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