Lipid transfer protein anchored at membrane contact sites 4, StARkin domain 2 (Lam4S2) (Lam4S2)

Lam4S2 is the second StARkin (also known as StART-like) domain of the yeast protein Lipid transfer protein anchored at membrane contact sites 4 (Lam4, or Ltc3), which belongs to the LAM/Ltc family of lipid transfer proteins. This domain is specialized for the non-vesicular transport of sterols between the endoplasmic reticulum and the plasma membrane at specific membrane contact sites [1, 2]. Structurally, it features a characteristic "helix-grip" fold that creates a deep hydrophobic pocket tailored to accommodate sterol molecules like ergosterol and cholesterol [1, 10]. Functionally, Lam4S2 acts as a lipid transporter by extracting sterols from a donor membrane and delivering them to an acceptor membrane, thereby maintaining cellular sterol distribution and membrane homeostasis [5, 11]. In yeast, the loss of Lam4 and its paralogs results in increased sensitivity to polyene antifungal drugs such as amphotericin B and nystatin, identifying these proteins as potential targets for therapeutic sensitization [2, 5]. Furthermore, Lam4S2 serves as a key model for its human orthologs, the GRAMD1 (Aster) proteins, which are implicated in cholesterol-related metabolic disorders and cancer progression [1, 8, 11].

Other names

Ltc3 StARkin domain 2Yhr080c StARkin domain 2StARkin domain 2 of Lam4StART-like domain-containing protein 3, domain 2Ltc3 SD2

Facilitates non-vesicular lipid transport by extracting sterol molecules into a hydrophobic pocket and transferring them between membranes at contact sites [1, 12].