Keuerleber Simon, Gsandtner Ingrid, Freissmuth Michael
Institute of Pharmacology, Medical University of Vienna, Austria.
Biochim Biophys Acta. 2011 May;1808(5):1350-7. doi: 10.1016/j.bbamem.2010.05.009. Epub 2010 May 15.
The extended carboxyl terminus of the A(2A)-adenosine receptor is known to engage several proteins other than those canonically involved in signalling by GPCRs (i.e., G proteins, G protein-coupled receptor kinases/GRKs, arrestins). The list includes the deubiquinating enzyme USP4, α-actinin, the guanine nucleotide exchange factor for ARF6 ARNO, translin-X-associated protein, calmodulin, the neuronal calcium binding protein NECAB2 and the synapse associated protein SAP102. However, if the fate of the A(2A)-receptor is taken into account - from its birthplace in the endoplasmic reticulum to its presumed site of disposal in the lysosome, it is evident that many more proteins must interact with the A(2A)-adenosine receptor. There are several arguments that support the conjecture that these interactions will preferentially occur with the carboxyl terminus of the A(2A)-adeonsine receptor: (i) the extended carboxyl terminus (of 122 residues=) offers the required space to accommodate companions; (ii) analogies can be drawn with other receptors, which engage several of these binding partners with their C-termini. This approach allows for defining the nature of the unknown territory. As an example, we posit a chaperone/coat protein complex-II (COPII) exchange model that must occur on the carboxyl terminus of the receptor. This model accounts for the observation that a minimum size of the C-terminus is required for correct folding of the receptor. It also precludes premature recruitment of the COPII-coat to a partially folded receptor.
已知A(2A)-腺苷受体的延长羧基末端能与几种蛋白质相互作用，这些蛋白质并非典型的参与G蛋白偶联受体（GPCR）信号传导的蛋白质（即G蛋白、G蛋白偶联受体激酶/GRKs、阻遏蛋白）。这些蛋白质包括去泛素化酶USP4、α-辅肌动蛋白、ARF6的鸟嘌呤核苷酸交换因子ARNO、转脂蛋白-X相关蛋白、钙调蛋白、神经元钙结合蛋白NECAB2和突触相关蛋白SAP102。然而，如果考虑A(2A)-受体的命运——从其在内质网的诞生地到其在溶酶体中的假定处置位点，显然还有更多蛋白质必须与A(2A)-腺苷受体相互作用。有几个论据支持这样的推测，即这些相互作用将优先发生在A(2A)-腺苷受体的羧基末端：(i) 延长的羧基末端（122个残基）提供了容纳伴侣所需的空间；(ii) 可以与其他受体进行类比，这些受体通过其C末端与其中一些结合伴侣相互作用。这种方法有助于定义未知领域的性质。例如，我们提出了一种必须在受体羧基末端发生的伴侣蛋白/II型被膜小泡蛋白复合体（COPII）交换模型。该模型解释了这样的观察结果，即受体的正确折叠需要C末端的最小尺寸。它还排除了COPII被膜过早招募到部分折叠的受体上的情况。
