Membrane binding domains

Hurley, James H.

doi:10.1016/j.bbalip.2006.02.020

Cited by 152 publications

(135 citation statements)

References 79 publications

(96 reference statements)

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“…In solution, it would be available for membrane binding. We speculated that these residues comprised either a docking site for another protein or, by analogy to other membrane-binding domains (3,17), a hydrophobic membrane anchor. Such anchor regions occurs on FYVE, C1, PX, and ENTH domains and others and increase affinity for membraneembedded lipids by allowing the protein itself to embed into the membrane (3,17).…”

Section: Resultsmentioning

confidence: 99%

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit

Bouřa

Hurley

2012

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

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MVB12-associated β-prism (MABP) domains are predicted to occur in a diverse set of membrane-associated bacterial and eukaryotic proteins, but their existence, structure, and biochemical properties have not been characterized experimentally. Here, we find that the MABP domains of the MVB12A and B subunits of ESCRT-I are functional modules that bind in vitro to liposomes containing acidic lipids depending on negative charge density. The MABP domain is capable of autonomously localizing to subcellular puncta and to the plasma membrane. The 1.3-Å atomic resolution crystal structure of the MVB12B MABP domain reveals a β-prism fold, a hydrophobic membrane-anchoring loop, and an electropositive phosphoinositide-binding patch. The basic patch is open, which explains how it senses negative charge density but lacks stereoselectivity. These observations show how ESCRT-I could act as a coincidence detector for acidic phospholipids and protein ligands, enabling it to function both in protein transport at endosomes and in cytokinesis and viral budding at the plasma membrane.HIV | protein structure | protein-membrane interactions | X-ray crystallography | subcellular localization T he concept of modular membrane-targeting domains is an important theme in the architecture of regulatory proteins and central to our current understanding of the subcellular localization of proteins (1-3). The best known of these modules include the PH, PX, FYVE, C1, C2, and ENTH domains (1-3). Each of these domains was initially proposed on the basis of bioinformatics analysis and subsequently confirmed by structural, biochemical, and cell biological approaches.A recent bioinformatics analysis (4) led to the identification of a putative membrane-targeted domain, termed the "MVB12-associated β-prism" (MABP) domain (4). MABP domains are found at the N termini of MVB12A and B, which are subunits of the human ESCRT-I complex (5). ESCRT complexes are responsible for the endosomal sorting of ubiquitinated membrane proteins into multivesicular bodies (MVBs) en route to their lysosomal degradation (6, 7). ESCRT-I in particular is also involved in plasma membrane functions in cytokinesis and the release of HIV-1 and other viruses (8). MABP domains are also found in many membrane-associated bacterial proteins and in the N-terminal region of human DENND4 isoforms. DENND4 proteins are Rab10 guanine nucleotide exchange factors that localize to a tubular Golgi-proximal membrane compartment (9).We set out to test the inference that MABP domains interact with membranes and found that the MVB12A and B MABP domains did. The crystal structure, solved at atomic resolution, showed that the MABP domain has a β-prism fold, consistent with the bioinformatics analysis. The structure identified a potential membrane-binding site, which we confirmed experimentally in vitro and in vivo. We found that the domain bound to liposomes according to the negative charge density of the membrane but with little specificity for particular lipid head groups. We went on to characterize the...

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Section: Resultsmentioning

confidence: 99%

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit

Bouřa

Hurley

2012

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

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“…My aim in this review is to introduce general principles governing the lipid binding and cellular localization of some of the lipid-binding domains. The description and examples used are selective, and I refer the reader to other compelling reviews (4,(9)(10)(11) Figure 1 summarizes some of the common properties of these lipid-binding domains. All intracellular membranes contain a varying degree of anionic lipids, and a majority of lipid-binding domains contain cationic surfaces, at least locally.…”

Section: : S299-s304mentioning

confidence: 99%

Lipid binding domains: more than simple lipid effectors

Stahelin

2009

Journal of Lipid Research

124

105

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The spatial and temporal regulation of lipid molecules in cell membranes is a hallmark of cellular signaling and membrane trafficking events. Lipid-mediated targeting provides for strict control and versatility, because cell membranes harbor a large number of lipid molecules with variation in head group and acyl chain structures. Signaling and trafficking proteins contain a large number of modular domains that exhibit specific lipid binding properties and play a critical role in their localization and function. Nearly 20 years of research including structural, computational, biochemical and biophysical studies have demonstrated how these lipid-binding domains recognize their target lipid and achieve subcellular localization. The integration of this individual lipid-binding domain data in the context of the fulllength proteins, macromolecular signaling complexes, and the lipidome is only beginning to be unraveled and represents a target of therapeutic development. This review brings together recent findings and classical concepts to concisely summarize the lipid-binding domain field while illustrating where the field is headed and how the gaps may be filled in with new technologies.-Stahelin, R. V. Lipid binding domains: more than simple lipid effectors. J. Lipid Res. 2009. 50: S299-S304.

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“…The Spir proteins encode a modified FYVE zinc finger membrane-binding domain at the C-terminal end (Kerkhoff et al, 2001). FYVE zinc fingers are typically found in proteins involved in membrane trafficking (Hurley, 2006). Early on after the discovery of Spir proteins, transient expression studies in NIH 3T3 fibroblast cells showed that the actin nucleators accumulate at vesicle membranes where they induce the accumulation of filamentous actin (Otto et al, 2000).…”

Section: Functional Cooperation Of Spir/ Formin-2 Rab11 and Myosin mentioning

confidence: 99%

Structural and functional insights into the Spir/formin actin nucleator complex

Dietrich

Weiß

Pleiser

et al. 2013

Biological Chemistry

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Abstract:The diversity of cellular actin functions is attained by the activation of actin nucleator complexes, which initiate the polymerization of actin monomers into a helical double-stranded filament at defined subcellular compartments. Next to actin functions at the cell membrane, including different forms of membrane protrusions and invaginations, actin dynamics at intracellular membranes has recently become a research focus. Experiments addressing the vesicle-associated Spir WH2 domain containing actin nucleators have provided novel mechanistic insights into the function of actin dynamics at intracellular membranes. Spir proteins are targeted by a modified FYVE zinc finger motif toward endosomal and vesicle membranes, where they interact and cooperate with the distinct nucleators of the FMN subfamily of formins in the nucleation of actin filaments. The function of the Spir/ formin actin nucleator complex is closely related to the Rab11 small G protein, which is a key regulator of recycling and exocytic transport processes. Together with the actin motor protein and Rab11 effector myosin Vb, Spir/ formin nucleated actin filaments mediate actin-dependent vesicle transport processes. Drosophila and mouse genetic studies as well as cell biology experiments point toward an important role of the Spir/formin complex in oocyte maturation and in the structure and signaling of the nervous system.

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Membrane binding domains

Cited by 152 publications

References 79 publications

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit

Lipid binding domains: more than simple lipid effectors

Structural and functional insights into the Spir/formin actin nucleator complex

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