Lipid dynamics and peripheral interactions of proteins with membrane surfaces

Kinnunen, Paavo K.J.; Kõiv, Anu; Lehtonen, Jukka; Rytömaa, Marjatta; Mustonen, Pekka

doi:10.1016/0009-3084(94)90181-3

Cited by 143 publications

(126 citation statements)

References 312 publications

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“…This conformation, and the predicted membrane-binding mode, are strikingly similar to those predicted in ''extended lipid'' phospholipid-cytochrome c models (41)(42)(43) and could be used to anchor other proteins to membranes as well (44). Although extrusion of the 2Ј-chain from lamellar membranes might intuitively be considered energetically expensive, a number of studies suggest this can actually relieve conformational stress caused by lipids with propensities for negative membrane curvature (41). Conformational dynamic studies also suggest that the 2Ј-chain is specifically favored for extrusion from the bilayer (44), and fluorescence quenching experiments indicate that the 2Ј-acyl chain of a brominated phospholipid is sequestered by cytochrome c upon binding to liposomes (43).…”

Section: )supporting

confidence: 70%

“…It is noteworthy that the lipid chains of PI(4,5)P 2 extend in opposite directions, with the 1Ј-chain inserted into the lipid bilayer and the 2Ј-chain sequestered by the protein. This conformation, and the predicted membrane-binding mode, are strikingly similar to those predicted in ''extended lipid'' phospholipid-cytochrome c models (41)(42)(43) and could be used to anchor other proteins to membranes as well (44). Although extrusion of the 2Ј-chain from lamellar membranes might intuitively be considered energetically expensive, a number of studies suggest this can actually relieve conformational stress caused by lipids with propensities for negative membrane curvature (41).…”

Section: )supporting

confidence: 56%

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Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly

Saad

Miller

Tai

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

501

770

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During the late phase of HIV type 1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to the plasma membrane of most hematopoietic cell types, where they colocalize at lipid rafts and assemble into immature virions. Membrane binding is mediated by the matrix (MA) domain of Gag, a 132-residue polypeptide containing an N-terminal myristyl group that can adopt sequestered and exposed conformations. Although exposure is known to promote membrane binding, the mechanism by which Gag is targeted to specific membranes has yet to be established . Here we show that PI(4,5)P 2 binds directly to HIV-1 MA, inducing a conformational change that triggers myristate exposure. Related phosphatidylinositides PI, PI(3)P, PI(4)P, PI(5)P, and PI(3,5)P 2 do not bind MA with significant affinity or trigger myristate exposure. Structural studies reveal that PI(4,5)P 2 adopts an ''extended lipid'' conformation, in which the inositol head group and 2-fatty acid chain bind to a hydrophobic cleft, and the 1-fatty acid and exposed myristyl group bracket a conserved basic surface patch previously implicated in membrane binding. Our findings indicate that PI(4,5)P 2 acts as both a trigger of the myristyl switch and a membrane anchor and suggest a potential mechanism for targeting Gag to membrane rafts. matrix protein ͉ membrane targeting ͉ NMR ͉ lipid rafts

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Section: )supporting

confidence: 70%

Section: )supporting

confidence: 56%

Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly

Saad

Miller

Tai

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

501

770

View full text Add to dashboard Cite

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“…While the results presented here define a narrow interval between unaffected and affected steps in replication complex assembly and function, the precise nature of the replication block remains to be determined. Fluid membranes and specific lipids are required to activate some protein functions and to facilitate formation or modulation of protein-protein interactions (18,19). For example, UFA-containing lipids activate the membrane-associated Escherichia coli DNA replication initiator protein DnaA (8).…”

Section: Discussionmentioning

confidence: 99%

Membrane Synthesis, Specific Lipid Requirements, and Localized Lipid Composition Changes Associated with a Positive-Strand RNA Virus RNA Replication Protein

Lee

Ahlquist

2003

J Virol

102

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Multifunctional RNA replication protein 1a of brome mosaic virus (BMV), a positive-strand RNA virus, localizes to the cytoplasmic face of endoplasmic reticulum (ER) membranes and induces ER lumenal spherules in which viral RNA synthesis occurs. We previously showed that BMV RNA replication in yeast is severely inhibited prior to negative-strand RNA synthesis by a single-amino-acid substitution in the ole1w allele of yeast ⌬9 fatty acid (FA) desaturase, which converts saturated FAs (SFAs) to unsaturated FAs (UFAs). Here we further define the relationships between 1a, membrane lipid composition, and RNA synthesis. We show that 1a expression increases total membrane lipids in wild-type (wt) yeast by 25 to 33%, consistent with recent results indicating that the numerous 1a-induced spherules are enveloped by invaginations of the outer ER membrane. 1a did not alter total membrane lipid composition in wt or ole1w yeast, but the ole1w mutation selectively depleted 18-carbon, monounsaturated (18:1) FA chains and increased 16:0 SFA chains, reducing the UFA-to-SFA ratio from ϳ2.5 to ϳ1.5. Thus, ole1w inhibition of RNA replication was correlated with decreased levels of UFA, membrane fluidity, and plasticity. The ole1w mutation did not alter 1a-induced membrane synthesis, 1a localization to the perinuclear ER, or colocalization of BMV 2a polymerase, nor did it block spherule formation. Moreover, BMV RNA replication templates were still recovered from cell lysates in a 1a-induced, 1a-and membrane-associated, and nuclease-resistant but detergent-susceptible state consistent with spherules. However, unlike nearby ER membranes, the membranes surrounding spherules in ole1w cells were not distinctively stained with osmium tetroxide, which interacts specifically with UFA double bonds. Thus, in ole1w cells, spherule-associated membranes were locally depleted in UFAs. This localized UFA depletion helps to explain why BMV RNA replication is more sensitive than cell growth to reduced UFA levels. The results imply that 1a preferentially interacts with one or more types of membrane lipids.The RNA replication complexes of all well-studied, eukaryotic positive-strand RNA viruses are found on intracellular membranes. In association with RNA replication, infection by such viruses often induces proliferation, vesiculation, and sometimes redistribution of specific intracellular membranes (6,10,11,20,22,23,25,32,35,36,39,40,42). RNA replication by poliovirus, Semliki Forest virus, and cowpea mosaic virus is sensitive to cerulenin, a lipid synthesis inhibitor, implying a requirement for lipid and/or membrane synthesis (5, 12, 30). Brefeldin A, an inhibitor of secretory vesicle formation, blocks RNA replication by poliovirus and rhinovirus (24). Furthermore, in vitro studies show that some steps of positive-strand RNA virus RNA replication are sensitive to membrane-disrupting, nonionic detergents or are activated by added membrane lipids (3,44,47). Nevertheless, present knowledge of the contributions of membranes to the assembly and function of ...

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“…It has become widely accepted that regions of biological membranes exist which are highly specialized and which are enriched in specific proteins and lipids [88][89][90][91][92][93][94][95][96][97][98][99][100][101][102]. Microdomain organization may be driven by lipid-protein and/or by lipid/lipid interactions.…”

Section: Organization Of Cholesterol In Disk Membranesmentioning

confidence: 99%

The role of cholesterol in rod outer segment membranes

Albert

Boesze‐Battaglia

2005

Progress in Lipid Research

108

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The photoreceptor rod outer segment (ROS) provides a unique system in which to investigate the role of cholesterol, an essential membrane constituent of most animal cells. The ROS is responsible for the initial events of vision at low light levels. It consists of a stack of disk membranes surrounded by the plasma membrane. Light capture occurs in the outer segment disk membranes that contain the photopigment, rhodopsin. These membranes originate from evaginations of the plasma membrane at the base of the outer segment. The new disks separate from the plasma membrane and progressively move up the length of the ROS over the course of several days. Thus the role of cholesterol can be evlauated in two distinct membranes. Furthermore, because the disk membranes vary in age it can also be investigated in a membrane as a function of the membrane age. The plasma membrane is enriched in cholesterol and in saturated fatty acids species relative to the disk membrane. The newly formed disk membranes have 6-fold more cholesterol than disks at the apical tip of the ROS. The partitioning of cholesterol out of disk membranes as they age and are apically displaced is consistent with the high PE content of disk membranes relative to the plasma membrane. The cholesterol composition of membranes has profound consequences on the major protein, rhodopsin. Biophysical studies in both model membranes and in native membranes have demonstrated that cholesterol can modulate the activity of rhodopsin by altering the membrane hydrocarbon environment. These studies suggest that mature disk membranes initiate the visual signal cascade more effectively than the newly synthesized, high cholesterol basal disks. Although rhodopsin is also the major protein of the plasma membrane, the high membrane cholesterol content inhibits rhodopsin participation in the visual transduction cascade. In addition to its effect on the hydrocarbon region, cholesterol may interact directly with rhodopsin. While high cholesterol inhibits rhodopsin activation, it also stabilizes the protein to denaturation. Therefore the disk membrane must perform a balancing act providing sufficient cholestrol to confer stability but without making the membrane too restrictive to receptor activation. Within a given disk membrane, it is likely that cholesterol exhibits an asymmetric distribution between the inner and outer bilayer leaflets. Furthremore, there is some evidence of cholesterol microdomains in the disk membranes. The availability of the disk protein, rom-1 may be sensitive to membrane cholesterol. The effects exerted by cholesterol on rhodopsin function have far-reaching implications for the study of G-protein coupled receptors as a whole. These studies show that the function of a membrane receptor can be modulated by modification of HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript the lipid bilayer, particularly cholesterol. This provides a powerful means of fine-tuning the activity of a membrane protein without resorting ...

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Lipid dynamics and peripheral interactions of proteins with membrane surfaces

Cited by 143 publications

References 312 publications

Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly

Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly

Membrane Synthesis, Specific Lipid Requirements, and Localized Lipid Composition Changes Associated with a Positive-Strand RNA Virus RNA Replication Protein

The role of cholesterol in rod outer segment membranes

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