TIA1, a protein critical for eukaryotic stress response and stress granule formation, is structurally characterized in full-length form. TIA1 contains three RNA recognition motifs (RRMs) and a C-terminal low-complexity domain, sometimes referred to as a “prion-related domain” or associated with amyloid formation. Under mild conditions, full-length (fl) mouse TIA1 spontaneously oligomerizes to form a metastable colloid-like suspension. RRM2 and RRM3, known to be critical for function, are folded similarly in excised domains and this oligomeric form of apo fl TIA1, based on NMR chemical shifts. By contrast, the termini were not detected by NMR and are unlikely to be amyloid-like. We were able to assign the NMR shifts with the aid of previously assigned solution-state shifts for the RRM2,3 isolated domains and homology modeling. We present a micellar model of fl TIA1 wherein RRM2 and RRM3 are colocalized, ordered, hydrated, and available for nucleotide binding. At the same time, the termini are disordered and phase separated, reminiscent of stress granule substructure or nanoscale liquid droplets.

TIA1 是一种对真核生物应激反应和应激颗粒形成至关重要的蛋白质，在结构上以全长形式表征。TIA1 包含三个 RNA 识别基序 (RRM) 和一个 C 端低复杂性结构域，有时称为“朊病毒相关结构域”或与淀粉样蛋白形成相关。在温和条件下，全长 (fl) 小鼠 TIA1 自发寡聚化形成亚稳态胶体样悬浮液。基于 NMR 化学位移，已知对功能至关重要的 RRM2 和 RRM3 在切除域和这种 apo fl TIA1 的寡聚形式中类似地折叠。相比之下，核磁共振未检测到末端，不太可能是淀粉样蛋白样。我们能够借助先前为 RRM2,3 隔离域和同源建模指定的溶液状态位移来指定 NMR 位移。我们提出了 fl TIA1 的胶束模型，其中 RRM2 和 RRM3 共定位、有序、水合并可用于核苷酸结合。同时，末端无序且相分离，让人联想到应力颗粒亚结构或纳米级液滴。