6BAS

Crystal structure of Thermus thermophilus Rod shape determining protein RodA D255A mutant (Q5SIX3_THET8)

Summary for 6BAS

• Entry DOI: 10.2210/pdb6bas/pdb
• Related: 6BAR
• Descriptor: Peptidoglycan glycosyltransferase RodA, CHLORIDE ION (3 entities in total)
• Functional Keywords: peptidoglycan glycosyltransferase, transmembrane protein, shape elogation division and sporulation, elongasome, transferase
• Biological source: Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
• Total number of polymer chains: 1
• Total formula weight: 38680.42

Authors

Sjodt, M.,Brock, K.,Dobihal, G.,Rohs, P.D.A.,Green, A.G.,Hopf, T.A.,Meeske, A.J.,Marks, D.S.,Bernhardt, T.G.,Rudner, D.Z.,Kruse, A.C. (deposition date: 2017-10-15, release date: 2018-03-28, Last modification date: 2023-10-04)

Primary citation

Sjodt, M.,Brock, K.,Dobihal, G.,Rohs, P.D.A.,Green, A.G.,Hopf, T.A.,Meeske, A.J.,Srisuknimit, V.,Kahne, D.,Walker, S.,Marks, D.S.,Bernhardt, T.G.,Rudner, D.Z.,Kruse, A.C.
Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis.
Nature, 556:118-121, 2018

PubMed Abstract: The shape, elongation, division and sporulation (SEDS) proteins are a large family of ubiquitous and essential transmembrane enzymes with critical roles in bacterial cell wall biology. The exact function of SEDS proteins was for a long time poorly understood, but recent work has revealed that the prototypical SEDS family member RodA is a peptidoglycan polymerase-a role previously attributed exclusively to members of the penicillin-binding protein family. This discovery has made RodA and other SEDS proteins promising targets for the development of next-generation antibiotics. However, little is known regarding the molecular basis of SEDS activity, and no structural data are available for RodA or any homologue thereof. Here we report the crystal structure of Thermus thermophilus RodA at a resolution of 2.9 Å, determined using evolutionary covariance-based fold prediction to enable molecular replacement. The structure reveals a ten-pass transmembrane fold with large extracellular loops, one of which is partially disordered. The protein contains a highly conserved cavity in the transmembrane domain, reminiscent of ligand-binding sites in transmembrane receptors. Mutagenesis experiments in Bacillus subtilis and Escherichia coli show that perturbation of this cavity abolishes RodA function both in vitro and in vivo, indicating that this cavity is catalytically essential. These results provide a framework for understanding bacterial cell wall synthesis and SEDS protein function.

PubMed: 29590088
DOI: 10.1038/nature25985

Experimental method

X-RAY DIFFRACTION (3.194 Å)