Can we identify the forces that drive the folding of integral membrane proteins?

Booth, Paula J.; Templer, Richard H.; Curran, A R; Allen, Sarah

doi:10.1042/bst0290408

Cited by 14 publications

(10 citation statements)

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“…Significantly, the latter process was directly regulated by varying the membrane lipid compositon. A similar result was obtained for the integral membrane proteins bacteriorhodopsin and the OmpA protein of Escherichia coli (Booth et al, 2001). These two in vitro studies demonstrated that "overall [protein] folding efficiency seem[s] to be controlled by particular properties of the lipid bilayer‰.…”

supporting

confidence: 68%

Neuromolecular Computing in Brain Evolution: Models and Methods

Wallace¹

2007

Neuroquantology

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Abstract Abstract This article presents a rationale and suggests possible protocols for investigating evolutionary models of neuromolecular computing in humans and other animals. It begins with an historical overview of membrane and cytoskeleton models of possible computational relevance. A model of molecular computing in neurons is then presented. Its fundamental physical feature is a lateral concentration gradient of neural membrane lipids in an applied field during ion movement. It is proposed that electrostatic interactions between aligned and polarized ethenes of membrane-lipid diacyls and the charged amino-acid residues in an unfolded ion-channel protein regulate the rate of protein folding (ion-channel closing). In this manner, lipid-protein electrostatic interactions regulate neuron signaling. Suggested experimental protocols emphasizing fluorescence and ultrafast x-ray diffraction analyses of membrane models (micelles) based on tissue samples from different species are described at length. It is concluded that research of this type could add a valuable molecular dimension to classic neuroanatomical approaches traditionally pursued in evolutionary studies.

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confidence: 68%

Neuromolecular Computing in Brain Evolution: Models and Methods

Wallace¹

2007

Neuroquantology

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“…The experimental determination of folding pathways in membrane proteins has lagged behind that of soluble proteins because the presence of lipids or detergents complicate both the experimental setup and the interpretation of folding studies of membrane proteins (44,45). Additionally, the higher stability of TM helices compared with soluble helices often prevents their denaturation (46). Only two proteins have been refolded from a completely unfolded state: bacteriorhodopsin (47), which also contains seven-TM helices, and OmpA (48), a ␤-barrel protein.…”

Section: Discussionmentioning

confidence: 99%

Identification of core amino acids stabilizing rhodopsin

Rader

Anderson²,

Isin³

et al. 2004

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

148

170

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Rhodopsin is the only G protein-coupled receptor (GPCR) whose 3D structure is known; therefore, it serves as a prototype for studies of the GPCR family of proteins. Rhodopsin dysfunction has been linked to misfolding, caused by chemical modifications that affect the naturally occurring disulfide bond between C110 and C187. Here, we identify the structural elements that stabilize rhodopsin by computational analysis of the rhodopsin structure and comparison with data from previous in vitro mutational studies. We simulate the thermal unfolding of rhodopsin by breaking the native-state hydrogen bonds sequentially in the order of their relative strength, using the recently developed Residues most stable under thermal denaturation are part of a core, which is assumed to be important for the formation and stability of folded rhodopsin. This core includes the C110OC187 disulfide bond at the center of residues forming the interface between the transmembrane and the extracellular domains near the retinal binding pocket. Fast mode analysis of rhodopsin using the Gaussian network model also identifies the disulfide bond and the retinal ligand binding pocket to be the most rigid region in rhodopsin. Experiments confirm that 90% of the amino acids predicted by the FIRST method to be part of the core cause misfolding upon mutation. The observed high degree of conservation (78.9%) of this disulfide bond across all GPCR classes suggests that it is critical for the stability and function of GPCRs.network models ͉ membrane protein ͉ folding ͉ G protein-coupled receptor ͉ simulation R hodopsin is the only member of the G protein-coupled receptors (GPCRs), the largest family of cell-surface receptors, whose 3D structure is known (1). The signature motif of the GPCR family is a bundle of seven-transmembrane (TM) helices connected by polypeptide loops that form the cytoplasmic (CP) and the extracellular (EC) domains on opposite sides of the TM domain (Fig. 1). GPCRs perform extremely diverse and vital functions that include responses to light, odor, taste, neurotransmitters, hormones, and a variety of other signals (2). Whereas, in rhodopsin and related visual pigments, the ligand 11-cisretinal (RET) is covalently bound to the apoproteins (opsins), all other GPCRs occur in the ligand-free form, and subsequent binding of appropriate ligand(s) results in their activation. There is a wide variation in the nature of the ligands and their binding modes such as direct binding to the TM domain, the EC domain, or both.Based on pharmacological specificity and sequence conservation, GPCRs are divided into eight classes (3). Although there is no sequence homology between GPCRs in different classes, the seven-TM helix motif is conserved throughout, and all GPCRs share a common topology. They can be grouped into three main classes: receptors related to rhodopsins (class A), secretin receptors (class B), and the metabotropic neurotransmitter receptors (class C). Of these, class A, the largest class, contains Ͼ1,200 distinct members and Ͼ7,000 putat...

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“…There are four kinds of retinal (rhodopsin-like) proteins in the membrane of archaeal bacteria: bacteriorhodopsin (BR), halorhodopsin (HR), sensory rhodopsin I (sRI) and phoborhodopsin (pR, also called sensory rhodopsin II, sRII) (1). The former two act as light-driven ion pumps (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) while the latter two are photosensory receptors (12)(13)(14)(15)(16)(17). These four retinal proteins have the same tertiary structure, in which they have seven transmembrane-helices and a retinal chromophore bound to a conserved lysine residue on the seventh helix (G-helix) via a protonated Schiff base.…”

Section: Introductionmentioning

confidence: 99%

Halorhodopsin from Natronomonas pharaonis Forms a Trimer Even in the Presence of a Detergent, Dodecyl‐β‐d‐maltoside

Sasaki

Kubo

Kikukawa

et al. 2009

Photochem & Photobiology

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Halorhodopsin (HR) is a transmembrane seven-helix retinal protein, and acts as an inward light-driven Cl ) pump. HR from Natronomonas pharaonis (NpHR) can be expressed in Escherichia coli inner membrane in large quantities. Here, we showed that NpHR forms the trimer structure even in the presence of, whose concentrations are much higher than the critical micelle concentration (0.17 mM M). This conclusion was drawn from the following observations. (1) NpHR in the DDM solution showed an exciton-coupling circular dichroism (CD) spectrum. (2) From the elution volume of gel filtration, the molecular mass of the NpHR-DDM complex was estimated. After evaluation of the mass of the bound DDM molecules, the mass of NpHR calculated was approximately equal to that of the trimer. (3) The cross-linked NpHR by glutaraldehyde gave the SDS-PAGE corresponding to the trimer. Mass spectra of these samples also support the notion of the trimer. Using the membrane fractions expressing NpHR (Escherichia coli and Halobacterium salinarum), CD spectra showed excitoncoupling, which suggests strongly the trimer structure in the cell membrane.

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Can we identify the forces that drive the folding of integral membrane proteins?

Cited by 14 publications

References 1 publication

Neuromolecular Computing in Brain Evolution: Models and Methods

Neuromolecular Computing in Brain Evolution: Models and Methods

Identification of core amino acids stabilizing rhodopsin

Halorhodopsin from Natronomonas pharaonis Forms a Trimer Even in the Presence of a Detergent, Dodecyl‐β‐d‐maltoside

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