CSIR Central

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

IR@IMTECH: CSIR-Institute of Microbial Technology, Chandigarh


Field	Value

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

Creator	Choukate, Komal Chaudhuri, Barnali

Subject	QR Microbiology

Description	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 angstrom 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 available data are suggested.

Publisher	INT UNION CRYSTALLOGRAPHY

Date	2020-07-08

Type	Article PeerReviewed

Relation	https://journals.iucr.org/m/issues/2020/04/00/lz5036/ http://crdd.osdd.net/open/2586/

Identifier	Choukate, Komal and Chaudhuri, Barnali (2020) Structural basis of self-assembly in the lipid-binding domain of mycobacterial polar growth factor Wag31. IUCRJ, 7 (4). pp. 767-776.