资源环境科技发展态势分析平台

Massive disk galaxies like the Milky Way are expected to form at late times in traditional models of galaxy formation(1,2), but recent numerical simulations suggest that such galaxies could form as early as a billion years after the Big Bang through the accretion of cold material and mergers(3,4). Observationally, it has been difficult to identify disk galaxies in emission at high redshift(5,6) in order to discern between competing models of galaxy formation. Here we report imaging, with a resolution of about 1.3 kiloparsecs, of the 158-micrometre emission line from singly ionized carbon, the far-infrared dust continuum and the near-ultraviolet continuum emission from a galaxy at a redshift of 4.2603, identified by detecting its absorption of quasar light. These observations show that the emission arises from gas inside a cold, dusty, rotating disk with a rotational velocity of about 272 kilometres per second. The detection of emission from carbon monoxide in the galaxy yields a molecular mass that is consistent with the estimate from the ionized carbon emission of about 72 billion solar masses. The existence of such a massive, rotationally supported, cold disk galaxy when the Universe was only 1.5 billion years old favours formation through either cold-mode accretion or mergers, although its large rotational velocity and large content of cold gas remain challenging to reproduce with most numerical simulations(7,8).

A massive rotating disk galaxy was formed a mere 1.5 billion years after the Big Bang, a surprisingly short time after the origin of the Universe.

After activation by an agonist, G-protein-coupled receptors (GPCRs) recruit beta-arrestin, which desensitizes heterotrimeric G-protein signalling and promotes receptor endocytosis(1). Additionally, beta-arrestin directly regulates many cell signalling pathways that can induce cellular responses distinct from that of G proteins(2). In contrast to G proteins, for which there are many high-resolution structures in complex with GPCRs, the molecular mechanisms underlying the interaction of beta-arrestin with GPCRs are much less understood. Here we present a cryo-electron microscopy structure of beta-arrestin 1 (beta arr1) in complex with M2 muscarinic receptor (M2R) reconstituted in lipid nanodiscs. The M2R-beta arr1 complex displays a multimodal network of flexible interactions, including binding of the N domain of beta arr1 to phosphorylated receptor residues and insertion of the finger loop of beta arr1 into the M2R seven-transmembrane bundle, which adopts a conformation similar to that in the M2R-heterotrimeric G(o) protein complex(3). Moreover, the cryo-electron microscopy map reveals that the C-edge of beta arr1 engages the lipid bilayer. Through atomistic simulations and biophysical, biochemical and cellular assays, we show that the C-edge is critical for stable complex formation, beta arr1 recruitment, receptor internalization, and desensitization of G-protein activation. Taken together, these data suggest that the cooperative interactions of beta-arrestin with both the receptor and the phospholipid bilayer contribute to its functional versatility.