Rhodopsin–transducin heteropentamer: Three-dimensional structure and biochemical characterization

Jastrzębska, Beata; Ringler, Philippe; Lodowski, David T.; Moiseenkova-Bell, Vera Y.; Golczak, Marcin; Müller, Shirley A.; Palczewski, Krzysztof; Engel, Andréas

doi:10.1016/j.jsb.2011.08.016

Cited by 52 publications

(90 citation statements)

References 38 publications

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“…For example, Whorton et al (37) demonstrated that monomeric ␤2-adrenergic receptor was able to mediate agonist-dependent nucleotide exchange from the G s heterotrimeric G-protein. However, recent studies by Jastrzebska et al (41,42) demonstrated that bovine rhodopsin purified from native tissues is functional as a heteropentamer existing of two receptors in complex with a heterotrimeric G-protein.…”

Section: Discussionmentioning

confidence: 99%

Protease-activated Receptor 1 (PAR1) and PAR4 Heterodimers Are Required for PAR1-enhanced Cleavage of PAR4 by α-Thrombin

Arachiche

Mumaw

Fuente

et al. 2013

Journal of Biological Chemistry

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Background: Protease-activated receptor 1 (PAR1) and PAR4 mediate thrombin signaling in platelets. Results: Mutations in transmembrane helix 4 (TM4) of PAR1 or PAR4 disrupts ␣-thrombin-induced heterodimerization and PAR1-assisted PAR4 cleavage. Conclusion: PAR1-PAR4 heterodimers are required for efficient PAR4 cleavage. Significance: The dimerization of PAR1 and PAR4 may impact the effectiveness of PAR1 antagonists.

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Section: Discussionmentioning

confidence: 99%

Protease-activated Receptor 1 (PAR1) and PAR4 Heterodimers Are Required for PAR1-enhanced Cleavage of PAR4 by α-Thrombin

Arachiche

Mumaw

Fuente

et al. 2013

Journal of Biological Chemistry

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“…1C), making the assignment of 4F2hc and LAT2 in the 3D map possible. As determined by scanning TEM mass measurement, unstained n-dodecyl-β-D-maltoside (DDM)-purified membrane proteins prepared in a conventional way for TEM are associated with >55 kDa of copurified endogenous lipids and DDM molecules (19). Thus, the total mass of the LAT2/lipid/DDM ternary complex plus the single TMD and the cytoplasmic N-terminal domain of 4F2hc containing the His-tag and the protease cleavage site (>120 kDa) is significantly larger than that of the 4F2hc-ED (∼50 kDa).…”

Section: Significancementioning

confidence: 99%

Structural bases for the interaction and stabilization of the human amino acid transporter LAT2 with its ancillary protein 4F2hc

Rosell

Meury

Álvarez-Marimon

et al. 2014

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

119

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Heteromeric amino acid transporters (HATs) are the unique example, known in all kingdoms of life, of solute transporters composed of two subunits linked by a conserved disulfide bridge. In metazoans, the heavy subunit is responsible for the trafficking of the heterodimer to the plasma membrane, and the light subunit is the transporter. HATs are involved in human pathologies such as amino acidurias, tumor growth and invasion, viral infection and cocaine addiction. However structural information about interactions between the heavy and light subunits of HATs is scarce. In this work, transmission electron microscopy and single-particle analysis of purified human 4F2hc/L-type amino acid transporter 2 (LAT2) heterodimers overexpressed in the yeast Pichia pastoris, together with docking analysis and crosslinking experiments, reveal that the extracellular domain of 4F2hc interacts with LAT2, almost completely covering the extracellular face of the transporter. 4F2hc increases the stability of the light subunit LAT2 in detergent-solubilized Pichia membranes, allowing functional reconstitution of the heterodimer into proteoliposomes. Moreover, the extracellular domain of 4F2hc suffices to stabilize solubilized LAT2. The interaction of 4F2hc with LAT2 gives insights into the structural bases for light subunit recognition and the stabilizing role of the ancillary protein in HATs.CD98hc | 4F2hc ectodomain H eteromeric amino acid transporters (HATs) are composed of two subunits, a heavy (SLC3 family) and a light subunit [SLC7 or L-type amino acid transporter (LAT) family] linked by a conserved disulfide bridge (1). HATs are amino acid exchangers (1), and this transport activity resides in the light subunit (2). The heavy subunit (either 4F2hc or rBAT) is essential for trafficking of the holotransporter to the plasma membrane (3, 4). In mammals, six transporters heterodimerize with 4F2hc, and only one heterodimerizes with rBAT. The rBAT/b 0,+ AT complex is a dimer of heterodimers in which the light subunit is required for proper rBAT folding and stability (5, 6). In contrast, 4F2hc-associated transporters are simple heterodimers (6), and possible stabilizing roles of the two subunits in the biogenesis of the heterodimer have not been described.HATs have major impacts on human health and are involved directly in amino acidurias (cystinuria and lysinuric protein intolerance), tumor cell growth, glioma invasion, Kaposi's sarcomaassociated herpesvirus infection, and cocaine relapse (1). In addition to the role of HATs in amino acid transport, 4F2hc heterodimers mediate β1-and β3-integrin signaling (7).Structural information about HATs is scarce (1). The heavy subunits are type II membrane N-glycoproteins with a single transmembrane domain (TMD), an intracellular N terminus, and a large extracellular C terminus with sequence homology with bacterial α-amylases. Indeed, the atomic structure of the extracellular domain (ED) of human 4F2hc (4F2hc-ED) is similar to that of bacterial glucosidases [i.e., a triose phosphate isomerase barr...

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“…Oligomers of G protein-coupled receptors have been inferred from their functionality in pharmacological assays and detected in biochemical and biophysical studies on various systems, from native membranes to preparations reconstituted from purified components (1)(2)(3)(4)(5)(6)(7)(8). Oligomers (9 -15) and monomers (16 -18) have been detected in live cells by means of receptors labeled with fluorescent or bioluminescent probes.…”

mentioning

confidence: 99%

Coupling of G Proteins to Reconstituted Monomers and Tetramers of the M2 Muscarinic Receptor

Redka

Morizumi

Elmslie

et al. 2014

Journal of Biological Chemistry

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Background:The allosteric interaction between agonists and guanylyl nucleotides reports on the interaction between G protein-coupled receptors and G proteins. Results: Such allostery differs in kind between reconstituted monomers and tetramers of the M 2 muscarinic receptor. Conclusion: Monomers and tetramers mediate allostery via different mechanisms. Significance: Only tetramers resemble muscarinic receptors in myocardial membranes in the nature of their sensitivity to guanylyl nucleotides.

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Rhodopsin–transducin heteropentamer: Three-dimensional structure and biochemical characterization

Cited by 52 publications

References 38 publications

Protease-activated Receptor 1 (PAR1) and PAR4 Heterodimers Are Required for PAR1-enhanced Cleavage of PAR4 by α-Thrombin

Protease-activated Receptor 1 (PAR1) and PAR4 Heterodimers Are Required for PAR1-enhanced Cleavage of PAR4 by α-Thrombin

Structural bases for the interaction and stabilization of the human amino acid transporter LAT2 with its ancillary protein 4F2hc

Coupling of G Proteins to Reconstituted Monomers and Tetramers of the M2 Muscarinic Receptor

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