8HQA

Crystal structure of the ectodomain of the MlaD protein from Escherichia coli in the resting state

Summary for 8HQA

• Entry DOI: 10.2210/pdb8hqa/pdb
• Descriptor: Intermembrane phospholipid transport system binding protein MlaD (2 entities in total)
• Functional Keywords: abc transporter, asymmetric protomer movement, central channel, gram-negative bacteria, mla system, transport, transport protein
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 3
• Total formula weight: 52387.04

Authors

Dutta, A.,Kanaujia, S.P. (deposition date: 2022-12-13, release date: 2024-01-10, Last modification date: 2024-05-15)

Primary citation

Dutta, A.,Kanaujia, S.P.
The Structural Features of MlaD Illuminate its Unique Ligand-Transporting Mechanism and Ancestry.
Protein J., 43:298-315, 2024

PubMed Abstract: The membrane-associated solute-binding protein (SBP) MlaD of the maintenance of lipid asymmetry (Mla) system has been reported to help the transport of phospholipids (PLs) between the outer and inner membranes of Gram-negative bacteria. Despite the availability of structural information, the molecular mechanism underlying the transport of PLs and the ancestry of the protein MlaD remain unclear. In this study, we report the crystal structures of the periplasmic region of MlaD from Escherichia coli (EcMlaD) at a resolution range of 2.3-3.2 Å. The EcMlaD protomer consists of two distinct regions, viz. N-terminal β-barrel fold consisting of seven strands (referred to as MlaD domain) and C-terminal α-helical domain (HD). The protein EcMlaD oligomerizes to give rise to a homo-hexameric ring with a central channel that is hydrophobic and continuous with a variable diameter. Interestingly, the structural analysis revealed that the HD, instead of the MlaD domain, plays a critical role in determining the oligomeric state of the protein. Based on the analysis of available structural information, we propose a working mechanism of PL transport, viz. "asymmetric protomer movement (APM)". Wherein half of the EcMlaD hexamer would rise in the periplasmic side along with an outward movement of pore loops, resulting in the change of the central channel geometry. Furthermore, this study highlights that, unlike typical SBPs, EcMlaD possesses a fold similar to EF/AMT-type beta(6)-barrel and a unique ancestry. Altogether, the findings firmly establish EcMlaD to be a non-canonical SBP with a unique ligand-transport mechanism.

PubMed: 38347327
DOI: 10.1007/s10930-023-10179-5

Experimental method

X-RAY DIFFRACTION (3.2 Å)