抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...

Brown Adipose Tissue: Function and Physiological Significance

From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites

A review of central 5-HT receptors and their function

Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human β2-adrenergic receptor–T4 lysozyme fusion protein bound to the partial inverse agonist carazolol at 2.4 angstrom resolution. The structure provides a high-resolution view of a human G protein–coupled receptor bound to a diffusible ligand. Ligand-binding site accessibility is enabled by the second extracellular loop, which is held out of the binding cavity by a pair of closely spaced disulfide bridges and a short helical segment within the loop. Cholesterol, a necessary component for crystallization, mediates an intriguing parallel association of receptor molecules in the crystal lattice. Although the location of carazolol in the β2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopsin as a template model for this large receptor family.

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High-Resolution Crystal Structure of an Engineered Human β2-Adrenergic G Protein–Coupled Receptor

Analysis of Protein Palmitoylation

High level expression of mammalian G protein alpha subunit Gq subtypes in Escherichia coli.

Slow transient potassium current activated by muscarinic receptors and GTP-ase deficient form of G alpha(q) in sympathetic neurones: Dualism with M-current inhibition.

FFA1 and FFA4, two G protein-coupled receptors that are activated by long chain fatty acids, play crucial roles in mediating many biological functions in the body. As a result, these fatty acid receptors have gained considerable attention due to their potential to be targeted for the treatment of type-2 diabetes. However, the relative contribution of canonical G protein-mediated signalling versus the effects of agonist-induced phosphorylation and interactions with β-arrestins have yet to be fully defined. Recently, several reports have highlighted the ability of β-arrestins and GRKs to interact with and modulate different functions of both FFA1 and FFA4, suggesting that it is indeed important to consider these interactions when studying the roles of FFA1 and FFA4 in both normal physiology and in different disease settings. Here, we discuss what is currently known and show the importance of understanding fully how β-arrestins and GRKs regulate the function of long chain fatty acid receptors.

/pdf/how-arrestins-and-grks-regulate-the-function-of-long-chain-3bvnqwju.pdf

How Arrestins and GRKs Regulate the Function of Long Chain Fatty Acid Receptors

Significance Although it is appreciated that members of the large family of rhodopsin-like cell surface receptors can form dimeric or larger protein complexes when expressed at high levels in cultured cells, their organizational state within native cells and tissues of the body is largely unknown. We assessed this in neurons of the central nervous system by replacing the M1 muscarinic acetylcholine receptor in mice with a form of this receptor with an added fluorescent protein. Receptor function was unaltered by this change, and the biophysical approach we used demonstrated that the receptor exists as a mixture of monomers and dimers or oligomers. Drug treatments that target this receptor promote its monomerization, which may have significance for receptor function.

/pdf/the-m1-muscarinic-receptor-is-present-in-situ-as-a-ligand-2lq1fpma.pdf

Graeme Milligan

Papers

Analysis of Protein Palmitoylation

High level expression of mammalian G protein alpha subunit Gq subtypes in Escherichia coli.

Slow transient potassium current activated by muscarinic receptors and GTP-ase deficient form of G alpha(q) in sympathetic neurones: Dualism with M-current inhibition.

How Arrestins and GRKs Regulate the Function of Long Chain Fatty Acid Receptors

The M1 muscarinic receptor is present in situ as a ligand-regulated mixture of monomers and oligomeric complexes