Tubular lipid binding proteins (TULIPs) growing everywhere

Abstract

Tubular lipid binding proteins (TULIPs) have become a focus of interest in the cell biology of lipid signalling, lipid traffic and membrane contact sites. Each tubular domain has an internal pocket with a hydrophobic lining that can bind a hydrophobic molecule such as a lipid. This allows TULIP proteins to carry lipids through the aqueous phase. TULIP domains were first found in a large family of extracellular proteins related to the bacterial permeability-inducing protein (BPI) and cholesterol ester transfer protein (CETP). Since then, the same fold and lipid transfer capacity have been found in SMP domains (so-called for their occurrence in synaptotagmin, mitochondrial and lipid binding proteins), which localise to intracellular membrane contact sites. Here the methods for identifying known TULIPs are described, and used to find previously unreported TULIPs, one in the silk polymer and another in prokaryotes illustrated by the E. coli protein YceB. The bacterial TULIP alters views on the likely evolution of the domain, suggesting its presence in the last universal common ancestor. The major function of TULIPs is to handle lipids, but we still do not know how they work in detail, or how many more remain to be discovered. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.

Diverse Mechanisms of CRISPR-Cas9 Inhibition by Type IIC Anti-CRISPR Proteins

“…AcrIIC2 adopts an a 1 b 1-6 a 2 fold, with the C-terminal long a helix inserted into the half-barrel structure formed by the six b strands (Figure 2A). A Dali server search revealed that AcrIIC2 monomer shares some structural similarity with the tubular lipidbinding proteins ( Figure S2F) (Wong and Levine, 2017;Jeong et al, 2017); however, the AcrIIC2 dimer represents a novel fold with no reported homologous structures. The dimerization of AcrIIC2 is mediated by a 1 , b 1 , b 2 , b 3 , and adjacent loops of both monomers through the formation of a compact hydrophobic core (Figures 2A and 2B).…”

Lipid transporter TMEM24/C2CD2L is a Ca 2+ -regulated component of ER–plasma membrane contacts in mammalian neurons

“…One class of lipid-transport modules found in intracellular proteins that function at membrane contact sites are SMP (synaptotagmin-like, mitochondrial and lipid-binding protein) domains (8)(9)(10)(11). These domains represent a branch within the superfamily of TULIP (tubular lipid-binding) domains that comprise members found both in intracellular and extracellular proteins (12).…”

Integrated regulation of the phosphatidylinositol cycle and phosphoinositide‐driven lipid transport at ER‐PM contact sites

“…Evidence for additional LTPs that operate at ER‐PM contact sites and possess functions related to the PtdIns cycle have recently emerged; including complex signaling‐related roles for the relatively promiscuous TUbular LIPid‐binding (TULIP) family of LTPs, which possesses synaptotagmin‐like mitochondrial lipid‐binding protein (SMP) LTDs . While the LTDs from both families of PITPs appear to function as monomeric shuttles for a restricted group of lipid isomers, SMP domains promiscuously transfer glycerophospholipids, showing little headgroup specificity, and are capable of forming dimeric complexes or perhaps even larger macromolecular assemblies .…”