7vr6
Crystal structure of MlaC from Escherichia coli in quasi-open stateCrystal structure of MlaC from Escherichia coli in quasi-open state
Structural highlights
FunctionMLAC_ECOLI Actively prevents phospholipid accumulation at the cell surface. Probably maintains lipid asymmetry in the outer membrane by retrograde trafficking of phospholipids from the outer membrane to the inner membrane. May transfer phospholipid across the periplasmic space and deliver it to the MlaFEDB complex at the inner membrane.[1] Publication Abstract from PubMedThe 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 A 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. MlaC belongs to a unique class of non-canonical substrate-binding proteins and follows a novel phospholipid-binding mechanism.,Dutta A, Prasad Kanaujia S J Struct Biol. 2022 Sep 7;214(4):107896. doi: 10.1016/j.jsb.2022.107896. PMID:36084896[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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