8.A.254. The MrdA/MrdB (PBP2/RodA) Complex for Synthesis and Positioning of Peptidoglycan (MrdAB) Family Peptidoglycan (PG) is synthetized during cell division and elongation. PG forms an extracellular polymer crucial for cellular viability, the synthesis of which is the target of many antibiotics. PG assembly requires a glycosyltransferase (GT) to generate a glycan polymer using a Lipid II substrate, which is then crosslinked to the existing PG via a transpeptidase (TP) reaction. A Shape, Elongation, Division and Sporulation (SEDS) GT enzyme and a Class B Penicillin Binding Protein (PBP) form the core of the multi-protein complex required for PG assembly. Nygaard et al. 2023 used single particle cryo-EM to determine the structure of a cell elongation-specific E. coli RodA-PBP2 (MrdBA) complex.The Lipid II binding sites were identofied, and a mechanism was propsed for Lipid II-dependent polymerization. This suggests how the movement of the glycan strand from the Lipid II polymerization site of RodA towards the TP site of PBP2, functionally linking these two central enzymatic activities, are required for cell wall peptidoglycan biosynthesis.
References:
Nygaard, R., C.L.B. Graham, M. Belcher Dufrisne, J.D. Colburn, J. Pepe, M.A. Hydorn, S. Corradi, C.M. Brown, K.U. Ashraf, O.N. Vickery, N.S. Briggs, J.J. Deering, B. Kloss, B. Botta, O.B. Clarke, L. Columbus, J. Dworkin, P.J. Stansfeld, D.I. Roper, and F. Mancia. (2023). Structural basis of peptidoglycan synthesis by E. coli RodA-PBP2 complex. Nat Commun 14: 5151.
Examples:
TC#	Name	Organismal Type	Example
8.A.254.1.1	The MrdAB (PBP2/RodA) complex for peptidoglycan synthesis and placement between the inner and outer membranes of Gram-negative bacteria (Nygaard et al. 2023). MdrA/PBP2 of 633 aas has 1 N-terminal TMS while MdrB/RodA of 370 aas has 9 TMSs in a 3 + 3 + 3 TMS arrangement.		MrdA/MrdB of E. coli