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The Lipopolysaccharide transport periplasmic protein LptA is an essential component of the Lpt pathway in Gram-negative bacteria, such as Escherichia coli, responsible for transporting lipopolysaccharide (LPS) from the inner membrane across the periplasm to the outer membrane. LptA forms a structural bridge by oligomerizing in a head-to-tail manner, interacting sequentially with LptC at the inner membrane complex and LptDE at the outer membrane translocon to facilitate LPS movement powered by ATP hydrolysis from the LptBFG complex. Its structure features a novel β-jellyroll fold of 16 antiparallel β-strands, which binds LPS in a hydrophobic pocket, inducing conformational changes like N-terminal unfolding and oligomer stabilization. Disruption of LptA leads to defective LPS transport, accumulation of anomalous LPS forms, periplasmic membrane abnormalities, and loss of outer membrane integrity, rendering bacteria hypersensitive to environmental stresses. As a bacterial-specific transporter critical for cell envelope biogenesis, LptA represents a potential therapeutic target for novel antibiotics against Gram-negative pathogens, though no approved drugs are known.
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