8.A.144.  The Nicalin (Nicalin) Family

McGilvray et al. 2020 described a ~ 360 kDa ribosome-associated complex comprising the core Sec61 channel (TC# 3.A.5.9.1) and five accessory factors: TMCO1 (TC# 1.A.106.1.1), CCDC47 (TC# 8.A.142.1.1) and the Nicalin (TC# 8.A.144.1.1)-TMEM147 (TC# 8.A.145.1.1)-NOMO2 (8.A.146.1.1) complex. Cryo-EM revealed a large assembly at the ribosome exit tunnel organized around a central membrane cavity. Similar to protein-conducting channels that facilitate movement of TMSs, cytosolic and luminal funnels in TMCO1 and TMEM147, respectively, suggested routes into the central membrane cavity. High-throughput mRNA sequencing showed selective translocon engagement with hundreds of different multi-pass membrane proteins. Consistent with a role in multi-pass membrane protein biogenesis, cells lacking different accessory components showed reduced levels of one such client, the glutamate transporter EAAT1 (TC# 2.A.23.2.6). These results identified a human translocon complex and provided a molecular framework for understanding its role in multi-pass membrane protein biogenesis (McGilvray et al. 2020).