8.A.35 The Mycobacterial Membrane Protein Small (MmpS) Family The MmpS family (mycobacterial membrane protein small) includes over 100 small membrane proteins specific to the genus Mycobacterium that have not yet been studied experimentally. The genes encoding MmpS proteins are often associated with mmpL genes, which are homologous to the RND (resistance nodulation cell division) genes of Gram-negative bacteria that encode proteins functioning as multidrug efflux system. Deshayes et al. (2010) showed by molecular genetics and biochemical analysis that MmpS4 in Mycobacterium smegmatis is required for the production and export of large amounts of cell surface glycolipids, but is dispensable for biosynthesis per se. MmpS4 is dispensable for transport to the surface. Orthologous complementation demonstrated that the MmpS4 proteins are exchangeable, thus not specific to a defined lipid species. MmpS4 function requires the formation of a protein complex at the pole of the bacillus, which requires the extracytosolic C-terminal domain of MmpS4. Deshayes et al. (2010) suggested that MmpS proteins facilitate lipid biosynthesis by acting as a scaffold for coupled biosynthesis and transport machinery.
This family belongs to the Ankyrin Repeat Domain-containing (Ank) Superfamily.
References:
Briffotaux, J., W. Huang, X. Wang, and B. Gicquel. (2017). MmpS5/MmpL5 as an efflux pump in Mycobacterium species. Tuberculosis (Edinb) 107: 13-19.
Deshayes, C., H. Bach, D. Euphrasie, R. Attarian, M. Coureuil, W. Sougakoff, F. Laval, Y. Av-Gay, M. Daffé, G. Etienne, and J.M. Reyrat. (2010). MmpS4 promotes glycopeptidolipids biosynthesis and export in Mycobacterium smegmatis. Mol. Microbiol. 78: 989-1003.
Gupta, K.R., C.M. Gwin, K.C. Rahlwes, K.J. Biegas, C. Wang, J.H. Park, J. Liu, B.M. Swarts, Y.S. Morita, and E.H. Rego. (2022). An essential periplasmic protein coordinates lipid trafficking and is required for asymmetric polar growth in mycobacteria. Elife 11:. [Epub: Ahead of Print]
Rego, E.H., R.E. Audette, and E.J. Rubin. (2017). Deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity. Nature 546: 153-157.
Wells, R.M., C.M. Jones, Z. Xi, A. Speer, O. Danilchanka, K.S. Doornbos, P. Sun, F. Wu, C. Tian, and M. Niederweis. (2013). Discovery of a siderophore export system essential for virulence of Mycobacterium tuberculosis. PLoS Pathog 9: e1003120.
Examples:
TC#	Name	Organismal Type	Example
8.A.35.1.1	MmpS4 protein	Gram-positive bacteria	*MmpS4 of Mycobacterium smegmatis* (A0QPN7)**

8.A.35.1.2	*MmpS5 auxillary protein; functions with MmpL5 in the export of siderophores (Wells et al.* 2013) and various drugs. Upregulation gives rise to antibiotic resistance (Briffotaux et al. 2017).**	Actinobacteria	MmpS5 of Mycobacterium tuberculosis

8.A.35.1.3	Uncharacterized protein of 180 aas and 1 TMS.		UP of Rhodococcus wratislaviensis

8.A.35.1.4	Uncharacterized protein of 161 aas and 1 TMS.		UP of Amycolatopsis decaplanina

8.A.35.1.5	Protein MmpS3 or LamA (Loss of asymmetry mutant A) of 299 aas with one very hydrophobic TMS at ~ residue 110. This protein is a component (subunit) of the complex involved in cell wall synthesis at the old pole. It is a mycobacterial divisome factor that when its gene is deleted, it collapses single-cell phenotypic heterogeneity (Rego et al. 2017). It coordinates lipid trafficking and is required for asymmetric polar growth in mycobacteria (Gupta et al. 2022).		LamA of Mycobacterium tuberculosis