Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Poster Session II

45-POS Board 21 Disordered Domains in Mycobacterium tuberculosis Membrane Proteins Associated with Cell Division Timothy A. Cross 1,2 , Jacob D. Moore 1,2 , Fei Huang 3 , A. Keith Dunker 3 . 1 National High Magnetic Field Lab, Tallahassee, FL, USA, 3 Indiana Univ. School of Medicine, Indianapolis, IN, USA. 2 Florida State University, Tallahassee, FL, USA, ChiZ of Mycobacterium tuberculosis (Mtb Rv2719c) is a small (164 amino acid residue) membrane protein having a single transmembrane helix, an N-terminus of 65 residues and a C- terminus of 78 residues. The TMHMM v2.0 prediction software on the Tuberculist website predicts that the N-terminus is in the periplasm and PONDR-FIT suggests that the N-terminus with 14 proline and 13 arginine residues is disordered. It has been functionally denoted as a peptidoglycan hydrolase and potentially this disorder is necessary for binding to the heterogeneous peptidoglycan layer of the cell wall. The cell wall is particularly complex in Mtb and during cell division it is critical for the bacillus to maintain the integrity of the cell wall. In part it is this cell wall that is responsible for the latent state of the bacillus that necessitates drug treatment over at least a 6 month period. Today there are rapidly increasing extreme drug resistant strains that are resistant to all of the front line drugs. As a result of the unique cell wall, many proteins involved in cell division are associated with hydrolyzing and reforming the cell wall including the peptidoglycan layer. Many of these proteins including FtsW, PonA1, PonA2, PbpB, RipA and ChiZ appear to have intrinsically disordered domains. Many other proteins involved in cell division including FtsK, Wag31, PknA, PknB, FtsQ, CwsA, Rv2164c are also predicted to have intrinsically disordered domains. Solution NMR spectra and spectral assignments of the N-terminal ChiZ domain in a disordered state have been obtained. Preliminary data in the presence of peptidoglycan will be shown. Solid- state NMR spectroscopy of lipid bilayer preparations and solution NMR spectroscopy in detergent micelles of CwsA will be shown leading to an initial structure of this Mtb cell division protein.

- 97 -