Solution structure studies of monomeric human TIP47/perilipin‐3 reveal a highly extended conformation

Hynson, Robert M.G.; Jeffries, Cy M.; Trewhella, Jill; Simon, Chantal

doi:10.1002/prot.24095

Cited by 18 publications

(30 citation statements)

References 51 publications

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“…This work additionally revealed a disordered N-terminal region and showed that the full-length protein assumes an extended conformation in solution, suggesting that the N and C termini might perform separate functions (3).…”

mentioning

confidence: 82%

“…Negative charge and negative spontaneous curvature both contribute to lipid binding for the C terminus of perilipin 3 For the C-terminal domain, negative charge is not the only driving factor for monolayer insertion, as the MIP and  max for POPG (anionic) are identical to those for POPC (zwitterionic), and both lipids have very small spontaneous curvatures (i.e., induce essentially no negative curvature stress in a lipid monolayer). Coupled with the results for POPA, POPE, and POG, this suggests that negative spontaneous curvature is important as well.…”

Section: The Amphipathic -Helix Bundle Of Perilipin 3 Inserts More Smentioning

confidence: 99%

“…Hynson et al (3) recently studied the structure of fulllength human perilipin 3 and showed that, as predicted by the crystal structure work, the protein has a highly helical C terminus in solution. This work additionally revealed a disordered N-terminal region and showed that the full-length protein assumes an extended conformation in solution, suggesting that the N and C termini might perform separate functions (3).…”

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confidence: 95%

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Insertion of perilipin 3 into a glycero(phospho)lipid monolayer depends on lipid headgroup and acyl chain species

Mirheydari

Rathnayake

Frederick

et al. 2016

Journal of Lipid Research

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function of LDs. While much work has focused on peripheral and integral membrane proteins, the mechanism by which LD binding proteins recognize and target to LDs is still poorly understood (1). This is especially true for dedicated LD binding proteins of the perilipin family, i.e., perilipin 1 through 5, that function in the biogenesis and metabolism (lipolysis) of LDs. No work has directly investigated the interaction of a perilipin family member with a phospholipid monolayer interface. In order to address how this family of proteins interacts with lipid interfaces, we investigated the interaction of perilipin 3 with phospholipid monolayers at the air-buffer interface. We chose perilipin 3 because it is found in the cytosol as well as on the LD surface, and because previous work has characterized the structure and LD association of the protein (1-3).In addition to providing cellular energy, LDs take part in many other cellular functions, including signal transduction, formation of new cellular membranes, hormone synthesis, and lipid trafficking (4-8). Under certain physiological conditions, LDs have been found to act as storehouses for several different types of enzymes and proteins, including histones (9, 10), and they also facilitate virus replication (11-13). An understanding of how proteins Lipid droplets (LDs) are dynamic cell organelles that carry out a multitude of cellular functions vital for life, and protein-lipid interactions are crucial to the structure and

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confidence: 82%

Section: The Amphipathic -Helix Bundle Of Perilipin 3 Inserts More Smentioning

confidence: 99%

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confidence: 95%

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Insertion of perilipin 3 into a glycero(phospho)lipid monolayer depends on lipid headgroup and acyl chain species

Mirheydari

Rathnayake

Frederick

et al. 2016

Journal of Lipid Research

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“…The Rab9 effector TIP47 binds the cytoplasmic domains of mannose-6-phosphate receptors (MPRs) in a Rab9-GTP-stimulated manner and is required for the return of this cargo to the Golgi complex (Carroll et al 2001). Because TIP47 is also involved in lipid droplet biogenesis under conditions of rapid fat storage, it remains to be determined if TIP47 might be a shared effector that also interacts with one of the myriad of Rab GTPases involved in lipid droplet formation or, alternatively, promotes interorganellar tethering to lipid droplets to allow access to critical lipid regulators of endocytosis Bulankina et al 2009;Hynson et al 2012). Indeed, Tip47 and Rab9 are important targets in viral infectivity and have been associated with lipid droplet consumption, suggesting that resolving this open question will be of significant interest (Murray et al 2005;Chen et al 2009b;Carvalho et al 2012;Vogt et al 2013).…”

Section: Rab Gtpases In Vesicle Buddingmentioning

confidence: 99%

Rab Proteins and the Compartmentalization of the Endosomal System

Wandinger‐Ness

Zerial

2014

Cold Spring Harbor Perspectives in Biology

509

469

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Of the approximately 70 human Rab GTPases, nearly three-quarters are involved in endocytic trafficking. Significant plasticity in endosomal membrane transport pathways is closely coupled to receptor signaling and Rab GTPase-regulated scaffolds. Here we review current literature pertaining to endocytic Rab GTPase localizations, functions, and coordination with regulatory proteins and effectors. The roles of Rab GTPases in (1) compartmentalization of the endocytic pathway into early, recycling, late, and lysosomal routes; (2) coordination of individual transport steps from vesicle budding to fusion; (3) effector interactomes; and (4) integration of GTPase and signaling cascades are discussed.

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“…X-ray crystallographic studies revealed that the C-terminal domain of TIP47 has a structure similar to that of the N-terminal domain of apolipoprotein E, suggesting a role for TIP47 in protein recruitment to lipid droplets and lipid biogenesis (20). TIP47 adopts an extended conformation in solution, suggesting that N-and C-terminal domains are well separated, perhaps facilitating independent functions of the two terminal regions (28).…”

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confidence: 99%

Reevaluation of the Requirement for TIP47 in Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Incorporation

Checkley

Luttge

Mercredi

et al. 2013

J Virol

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Incorporation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins into assembling particles is crucial for virion infectivity. Genetic and biochemical data indicate that the matrix (MA) domain of Gag and the cytoplasmic tail of the transmembrane glycoprotein gp41 play an important role in coordinating Env incorporation; however, the molecular mechanism and possible role of host factors in this process remain to be defined. Recent studies suggested that Env incorporation is mediated by interactions between matrix and tail-interacting protein of 47 kDa (TIP47; also known as perilipin-3 and mannose-6-phosphate receptor-binding protein 1), a member of the perilipin, adipophilin, TIP47 (PAT) family of proteins implicated in protein sorting and lipid droplet biogenesis. We have confirmed by nuclear magnetic resonance spectroscopy titration experiments and surface plasmon resonance that MA binds TIP47. We also reevaluated the role of TIP47 in HIV-1 Env incorporation in HeLa cells and in the Jurkat T-cell line. In HeLa cells, TIP47 overexpression or RNA interference (RNAi)-mediated depletion had no significant effect on HIV-1 Env incorporation, virus release, or particle infectivity. Similarly, depletion of TIP47 in Jurkat cells did not impair HIV-1 Env incorporation, virus release, infectivity, or replication. Our results thus do not support a role for TIP47 in HIV-1 Env incorporation or virion infectivity. Incorporation of the Env glycoprotein complex into assembling HIV-1 particles is critical for viral infectivity and replication. Env is synthesized as an ϳ160-kDa precursor polyprotein (gp160) in the endoplasmic reticulum (ER) and is processed into the mature surface glycoprotein gp120 and transmembrane glycoprotein gp41 during transport to virus assembly sites on the plasma membrane (1). Although many aspects of the HIV-1 assembly pathway have been deciphered over the past 2 decades (2, 3), the mechanism of Env recruitment and incorporation remains poorly understood. Several non-mutually exclusive models for Env incorporation have been suggested (1, 4): (i) an active model, in which Env is recruited through a direct interaction with the viral structural polyprotein Gag; (ii) a passive model, in which Env present at assembly sites is randomly incorporated; (iii) a Gag-Env cotargeting model, in which both Gag and Env localize to a common membrane microdomain to increase the local concentration of viral proteins at assembly sites; and (iv) an indirect Gag-Env interaction model, in which Env incorporation requires the formation of a ternary complex composed of Env, Gag, and a host cellular factor. The active model is supported by studies showing that mutations in the matrix protein (MA) or the gp41 cytoplasmic tail (CT) reduce levels of incorporation and that second-site compensatory mutations in MA can rescue other MA substitutions or a small gp41 CT deletion that blocks Env incorporation (5-11). The passive model for Env incorporation derives support from pseudotyping experiments, wherein foreig...

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Solution structure studies of monomeric human TIP47/perilipin‐3 reveal a highly extended conformation

Cited by 18 publications

References 51 publications

Insertion of perilipin 3 into a glycero(phospho)lipid monolayer depends on lipid headgroup and acyl chain species

Insertion of perilipin 3 into a glycero(phospho)lipid monolayer depends on lipid headgroup and acyl chain species

Rab Proteins and the Compartmentalization of the Endosomal System

Reevaluation of the Requirement for TIP47 in Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Incorporation

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