Structural basis of self-assembly in the lipid-binding domain of mycobacterial polar growth factor Wag31

IUCrJ
Komal Choukate, Barnali Chaudhuri

Abstract

Wag31, or DivIVA, is an essential protein and a drug target in the human pathogen Mycobacterium tuberculosis that self-assembles at the negatively curved membrane surface to form a higher-order structural scaffold, maintains rod-shaped cellular morphology and localizes key cell-wall synthesizing enzymes at the pole for exclusive polar growth. The crystal structure of the N-terminal lipid-binding domain of mycobacterial Wag31 was determined at 2.3 Å resolution. The structure revealed a highly polar surface lined with several conserved charged residues that suggest probable sites for interactions with membrane lipids. Crystal-packing analysis revealed a previously unseen 'dimer-of-dimers' assembly state of N-terminal Wag31, which is formed by antiparallel stacking of two coiled-coil dimers. Size-exclusion column-chromatography-coupled small-angle solution X-ray scattering data revealed a tetrameric form as a major assembly state of N-terminal Wag31 in solution, further supporting the crystal structure. The results suggest that, in addition to lipid binding, the N-terminal Wag31 can participate in self-assembly to form filamentous structures. Plausible models of linear self-assembly and branching of Wag31 filaments consistent with...Continue Reading

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Datasets Mentioned

BETA
SASDHH4

Methods Mentioned

BETA
super-resolution microscopy
X-ray
size-exclusion chromatography
size-exclusion column elution

Software Mentioned

CCP4MG
CLICK
TWISTER
PyMOL Molecular Graphics System
PDBePISA
REFMAC
Coot
MOLREP
XDS
ATSAS

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