TY - JOUR
T1 - Induced conformational changes activate the peptidoglycan synthase PBP1B
AU - Egan, Alexander J F
AU - Maya-Martinez, Roberto
AU - Ayala, Isabel
AU - Bougault, Catherine M
AU - Banzhaf, Manuel
AU - Breukink, Eefjan
AU - Vollmer, Waldemar
AU - Simorre, Jean-Pierre
N1 - This article is protected by copyright. All rights reserved.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Bacteria surround their cytoplasmic membrane with an essential, stress-bearing peptidoglycan (PG) layer consisting of glycan chains linked by short peptides into a mesh-like structure. Growing and dividing cells expand their PG layer using inner-membrane anchored PG synthases, including Penicillin-binding proteins (PBPs), which participate in dynamic protein complexes to facilitate cell wall growth. In Escherichia coli, and presumably other Gram-negative bacteria, growth of the mainly single layered PG is regulated by outer membrane-anchored lipoproteins. The lipoprotein LpoB is required to activate PBP1B, which is a major, bi-functional PG synthase with glycan chain polymerizing (glycosyltransferase) and peptide cross-linking (transpeptidase) activities. In this work we show how the binding of LpoB to the regulatory UB2H domain of PBP1B activates both activities. Binding induces structural changes in the UB2H domain, which transduce to the two catalytic domains by distinct allosteric pathways. We also show how an additional regulator protein, CpoB, is able to selectively modulate the TPase activation by LpoB without interfering with GTase activation. This article is protected by copyright. All rights reserved.
AB - Bacteria surround their cytoplasmic membrane with an essential, stress-bearing peptidoglycan (PG) layer consisting of glycan chains linked by short peptides into a mesh-like structure. Growing and dividing cells expand their PG layer using inner-membrane anchored PG synthases, including Penicillin-binding proteins (PBPs), which participate in dynamic protein complexes to facilitate cell wall growth. In Escherichia coli, and presumably other Gram-negative bacteria, growth of the mainly single layered PG is regulated by outer membrane-anchored lipoproteins. The lipoprotein LpoB is required to activate PBP1B, which is a major, bi-functional PG synthase with glycan chain polymerizing (glycosyltransferase) and peptide cross-linking (transpeptidase) activities. In this work we show how the binding of LpoB to the regulatory UB2H domain of PBP1B activates both activities. Binding induces structural changes in the UB2H domain, which transduce to the two catalytic domains by distinct allosteric pathways. We also show how an additional regulator protein, CpoB, is able to selectively modulate the TPase activation by LpoB without interfering with GTase activation. This article is protected by copyright. All rights reserved.
KW - Peptidoglycan
KW - Penicillin‐binding protein
KW - Lipoprotein
KW - NMR structure
KW - Allostery
U2 - 10.1111/mmi.14082
DO - 10.1111/mmi.14082
M3 - Article
C2 - 30044025
SN - 0950-382X
VL - 110
SP - 335
EP - 356
JO - Molecular Microbiology
JF - Molecular Microbiology
IS - 3
ER -