Lateral diffusion of peripheral membrane proteins on supported lipid bilayers is controlled by the additive frictional drags of (1) bound lipids and (2) protein domains penetrating into the bilayer hydrocarbon core

Ziemba, Brian P.; Falke, Joseph J.

doi:10.1016/j.chemphyslip.2013.04.005

Cited by 75 publications

(132 citation statements)

References 50 publications

(97 reference statements)

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“…The shallow insertion of MMP-12 among the head groups (Fig. 2) should reduce its frictional drag for faster translational diffusion across the membrane 52 . This could hasten collisions of MMP-12 with substrates or potential partners on membrane surfaces.…”

Section: Discussionmentioning

confidence: 99%

Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12

et al. 2014

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Matrix metalloproteinases (MMPs) regulate tissue remodeling, inflammation, and disease progression. Some soluble MMPs are inexplicably active near cell surfaces. Here, we demonstrate binding of MMP-12 directly to bilayers and cellular membranes using paramagnetic NMR and fluorescence. Opposing sides of the catalytic domain engage spin-labeled membrane mimics. Loops project from the β-sheet interface to contact the phospholipid bilayer with basic and hydrophobic residues. The distal membrane interface comprises loops on the other side of the catalytic cleft. Both interfaces mediate MMP-12 association with vesicles and cell membranes. MMP-12 binds plasma membranes and is internalized to hydrophobic perinuclear features, the nuclear membrane, and inside the nucleus within minutes. While binding of TIMP-2 to MMP-12 hinders membrane interactions beside the active site, TIMP-2-inhibited MMP-12 binds vesicles and cells, suggesting compensatory rotation of its membrane approaches. MMP-12 association with diverse cell membranes may target its activities to modulate innate immune responses and inflammation.

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Section: Discussionmentioning

confidence: 99%

Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12

et al. 2014

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“…13 Notably, this state might exhibit faster lateral diffusion than the PIP 3 -bound state and might diffuse even faster than free lipids in the bilayer, since the V278 penetration in the head group region would likely yield less friction against the bilayer than a lipid that penetrates deeply into the hydrocarbon region, 34 including the PIP 3 lipid that defines the single lateral diffusion rate of the PIP 3 -bound state. 20 However, the equilibrium affinity and bound state lifetime of this state must be small and transient, respectively, to ensure that membrane recruitment in the absence of the PIP 3 signal stays minimal since biological activation is provided purely by membrane recruitment.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of Membrane Binding of the GRP1 PH Domain

Lai

Srivastava

Pilling

et al. 2013

Journal of Molecular Biology

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The pleckstrin homology (PH) domain of the general receptor of phosphoinositides 1 (GRP1) protein selectively binds to a rare signaling phospholipid, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), in the membrane. The specific PIP3 lipid docking of GRP1 PH domain is essential to protein cellular function and is believed to occur in a stepwise process, electrostatic-driven membrane association followed by the specific PIP3 binding. By a combination of all-atom molecular dynamics (MD) simulations, coarse-grained analysis, electron paramagnetic resonance (EPR) membrane docking geometry, and fluorescence resonance energy transfer (FRET) kinetic studies, we have investigated the search and bind process in the GRP1 PH domain at the molecular scale. We simulated the two membrane binding states of the GRP1 PH domain in the PIP3 search process, before and after the GRP1 PH domain docks with the PIP3 lipid. Our results suggest that the background anionic phosphatidylserine lipids, which constitute around one-fifth of the membrane by composition, play a critical role in the initial stages of recruiting protein to the membrane surface through non-specific electrostatic interactions. Our data also reveal a previously unseen transient membrane association mechanism that is proposed to enable a two-dimensional “hopping” search of the membrane surface for the rare PIP3 target lipid. We further modeled the PIP3-bound membrane–protein system using the EPR membrane docking structure for the MD simulations, quantitatively validating the EPR membrane docking structure and augmenting our understanding of the binding interface with atomic-level detail. Several observations and hypotheses reached from our MD simulations are also supported by experimental kinetic studies.

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“…A precedent for this idea is the report that the dwell time of the PI(3,4,5)P 3 -specific PH-PLHC domain, measured by total internal reflection fluorescence (TIRF) microscopy on supported bilayers, increases in the presence of PI(3,4,5)P 3 and that the protein's surface diffusion rate is at the same order of magnitude as the diffusion rate of the lipid itself (71,72). In other words, in that system, the proteinmembrane interaction is so tight that the protein does not let go of the lipid on this time scale.…”

Section: Discussionmentioning

confidence: 99%

Membrane Binding of the Rous Sarcoma Virus Gag Protein Is Cooperative and Dependent on the Spacer Peptide Assembly Domain

Dick

Barros

Jin

et al. 2016

J Virol

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The principles underlying membrane binding and assembly of retroviral Gag proteins into a lattice are understood. However, little is known about how these processes are related. Using purified Rous sarcoma virus Gag and Gag truncations, we studied the interrelation of Gag-Gag interaction and Gag-membrane interaction. Both by liposome binding and by surface plasmon resonance on a supported bilayer, Gag bound to membranes much more tightly than did matrix (MA), the isolated membrane binding domain. In principle, this difference could be explained either by protein-protein interactions leading to cooperativity in membrane binding or by the simultaneous interaction of the N-terminal MA and the C-terminal nucleocapsid (NC) of Gag with the bilayer, since both are highly basic. However, we found that NC was not required for strong membrane binding. Instead, the spacer peptide assembly domain (SPA), a putative 24-residue helical sequence comprising the 12-residue SP segment of Gag and overlapping the capsid (CA) C terminus and the NC N terminus, was required. SPA is known to be critical for proper assembly of the immature Gag lattice. A single amino acid mutation in SPA that abrogates assembly in vitro dramatically reduced binding of Gag to liposomes. In vivo, plasma membrane localization was dependent on SPA. Disulfide cross-linking based on ectopic Cys residues showed that the contacts between Gag proteins on the membrane are similar to the known contacts in virus-like particles. Taken together, we interpret these results to mean that Gag membrane interaction is cooperative in that it depends on the ability of Gag to multimerize. IMPORTANCEThe retroviral structural protein Gag has three major domains. The N-terminal MA domain interacts directly with the plasma membrane (PM) of cells. The central CA domain, together with immediately adjoining sequences, facilitates the assembly of thousands of Gag molecules into a lattice. The C-terminal NC domain interacts with the genome, resulting in packaging of viral RNA. For assembly in vitro with purified Gag, in the absence of membranes, binding of NC to nucleic acid somehow facilitates further Gag-Gag interactions that lead to formation of the Gag lattice. The contributions of MA-mediated membrane binding to virus particle assembly are not well understood. Here, we report that in the absence of nucleic acid, membranes provide a platform that facilitates Gag-Gag interactions. This study demonstrates that the binding of Gag, but not of MA, to membranes is cooperative and identifies SPA as a major factor that controls this cooperativity. L ate in the retroviral life cycle, the structural protein Gag localizes to the inner leaflet of the plasma membrane (PM), where it assembles around the viral genomic RNA, leading to budding from the cell. Gag proteins include three major domains, the Nterminal matrix (MA) domain, which mediates membrane binding; the central capsid (CA) domain, which mediates Gag-Gag interactions during virion assembly; and the C-terminal nucleocapsid (NC...

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Lateral diffusion of peripheral membrane proteins on supported lipid bilayers is controlled by the additive frictional drags of (1) bound lipids and (2) protein domains penetrating into the bilayer hydrocarbon core

Cited by 75 publications

References 50 publications

Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12

Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12

Molecular Mechanism of Membrane Binding of the GRP1 PH Domain

Membrane Binding of the Rous Sarcoma Virus Gag Protein Is Cooperative and Dependent on the Spacer Peptide Assembly Domain

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