Biomolecular Spectroscopy and RUBiospek|NMR, Faculty of Chemistry and Biochemistry, Ruhr University of Bochum, Bochum, Germany.
Structural Genomics Consortium, Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Nat Commun. 2023 Apr 20;14(1):2273. doi: 10.1038/s41467-023-37705-4.
Bulky cargos like procollagens, apolipoproteins, and mucins exceed the size of conventional COPII vesicles. During evolution a process emerged in metazoans, predominantly governed by the TANGO1 protein family, that organizes cargo at the exit sites of the endoplasmic reticulum and facilitates export by the formation of tunnel-like connections between the ER and Golgi. Hitherto, cargo-recognition appeared to be mediated by an SH3-like domain. Based on structural and dynamic data as well as interaction studies from NMR spectroscopy and microscale thermophoresis presented here, we show that the luminal cargo-recognition domain of TANGO1 adopts a new functional fold for which we suggest the term MOTH (MIA, Otoraplin, TALI/TANGO1 homology) domain. These MOTH domains, as well as an evolutionary intermediate found in invertebrates, constitute a distinct domain family that emerged from SH3 domains and acquired the ability to bind collagen.
大体积货物，如原胶原蛋白、载脂蛋白和粘蛋白，超过了传统 COPII 囊泡的大小。在进化过程中，后生动物出现了一种主要由 TANGO1 蛋白家族控制的过程，该过程在内质网的出口部位组织货物，并通过在 ER 和高尔基体之间形成隧道样连接促进货物的输出。迄今为止，货物识别似乎是由一个 SH3 样结构域介导的。基于这里提出的结构和动态数据以及来自 NMR 光谱和微尺度热泳的相互作用研究，我们表明 TANGO1 的腔货物识别结构域采用了一种新的功能折叠，我们建议将其称为 MOTH（MIA、Otoraplin、TALI/TANGO1 同源）结构域。这些 MOTH 结构域以及在无脊椎动物中发现的进化中间体构成了一个独特的结构域家族，它起源于 SH3 结构域，并获得了结合胶原蛋白的能力。
