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Crystal structure of the PH-like domain of Lam6
Structural highlights
FunctionENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[1] LAM6_YEAST Involved in regulation of various organellar membrane contact sites (PubMed:26119743). May be involved in sterol transfer between intracellular membranes (PubMed:26001273). Selectively transports sterols between membranes in vitro. Involved in stress-dependent formation of sterol-enriched vacuolar membrane domains (PubMed:25987606).[2] [3] [4] Publication Abstract from PubMedMembrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs. Here, we determined the crystal structures of the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4 in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays a unique PH domain fold with a conserved N-terminal alpha-helix. The Lam6 PH-like domain lacks the basic surface for phosphoinositide binding, but contains hydrophobic patches on its surface, which are critical for targeting to endoplasmic reticulum (ER)-mitochondrial contacts. Structures of the LAM SDs display a helix-grip fold with a hydrophobic cavity and a flexible Omega1-loop as a lid. Ergosterol is bound to the pocket in a head-down orientation, with its hydrophobic acyl group located in the tunnel entrance. The Omega1-loop in an open conformation is essential for ergosterol binding by direct hydrophobic interaction. Structural comparison suggested that the sterol binding mode of the Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin superfamily. Structural models of full-length Lam2 correlated with the sterol transport function at the membrane contact sites. Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites.,Tong J, Manik MK, Im YJ Proc Natl Acad Sci U S A. 2018 Jan 16. pii: 1719709115. doi:, 10.1073/pnas.1719709115. PMID:29339490[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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