7VR6

Crystal structure of MlaC from Escherichia coli in quasi-open state

Summary for 7VR6

• Entry DOI: 10.2210/pdb7vr6/pdb
• Descriptor: Intermembrane phospholipid transport system binding protein MlaC, DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: abc transporter, periplasmic protein, membrane lipid asymmetry, segmented domain movement, mla transport system, transport protein
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 1
• Total formula weight: 23471.79

Authors

Dutta, A.,Kanaujia, S.P. (deposition date: 2021-10-21, release date: 2022-09-21, Last modification date: 2023-11-29)

Primary citation

Dutta, A.,Prasad Kanaujia, S.
MlaC belongs to a unique class of non-canonical substrate-binding proteins and follows a novel phospholipid-binding mechanism.
J.Struct.Biol., 214:107896-107896, 2022

PubMed Abstract: The outer membrane (OM) of Gram-negative bacteria acts as a formidable barrier against a plethora of detrimental compounds owing to its asymmetric nature. This is because the OM possesses lipopolysaccharides (LPSs) in the outer leaflet and phospholipids (PLs) in the inner leaflet. The maintenance of lipid asymmetry (Mla) system is involved in preserving the distribution of PLs in OM. The periplasmic component of the system MlaC serves as the substrate-binding protein (SBP) that shuttles PLs between the inner and outer membranes. However, an in-depth report highlighting its mechanism of ligand binding is still lacking. This study reports the crystal structure of MlaC from Escherichia coli (EcMlaC) at a resolution of 2.5 Å in a quasi-open state, complexed with PL. The structural analysis reveals that EcMlaC and orthologs comprise two major domains, viz. nuclear transport factor 2-like (NTF2-like) and phospholipid-binding protein (PBP). Each domain can be further divided into two subdomains arranged in a discontinuous fashion. This study further reveals that EcMlaC is polyspecific in nature and follows a reverse mechanism of the opening of the substrate-binding site during the ligand binding. Furthermore, MlaC can bind two PLs by forming subsites in the binding pocket. These findings, altogether, have led to the proposition of the unique "segmented domain movement" mechanism of PL binding, not reported for any known SBP to date. Further, unlike typical SBPs, MlaC has originated from a cystatin-like fold. Overall, this study establishes MlaC to be a non-canonical SBP with a unique ligand-binding mechanism.

PubMed: 36084896
DOI: 10.1016/j.jsb.2022.107896

Experimental method

X-RAY DIFFRACTION (2.5 Å)