Signal recognition particle receptor-β (SR-β) coordinates cotranslational N-glycosylation

被引:2
作者
Phoomak, Chatchai [1 ,2 ]
Rinis, Natalie [1 ]
Baro, Marta [1 ]
Shrimal, Shiteshu [3 ]
Bennett, Daniel [1 ]
Shaffer, Scott A. [3 ,4 ]
Lehrman, Mark [5 ]
Gilmore, Reid [3 ]
Contessa, Joseph N. [1 ,6 ]
机构
[1] Yale Sch Med, Dept Therapeut Radiol, New Haven, CT 06511 USA
[2] Chulalongkorn Univ, Fac Sci, Dept Biol, Bangkok 10330, Thailand
[3] Univ Massachusetts Chan Med Sch, Dept Biochem & Biotechnol, Worcester, MA 01605 USA
[4] Univ Massachusetts Chan Med Sch, Mass Spectrometry Facil, Shrewsbury, MA 01545 USA
[5] UT Southwestern Med Ctr Dallas, Dept Pharmacol, 6001 Forest Pk Rd, Dallas, TX 75390 USA
[6] Yale Sch Med, Dept Pharmacol, New Haven, CT 06511 USA
关键词
SUBUNIT; GTPASE; MEMBRANE; BINDING; COMPLEX; ER;
D O I
10.1126/sciadv.ade8079
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Proteins destined for the secretory compartment of the cell are cotranslationally translocated into the endoplasmic reticulum. The majority of these proteins are N-glycosylated, a co- and posttranslational modification that ensures proper protein folding, stability, solubility, and cellular localization. Here, we show that the beta subunit of the signal recognition particle receptor (SR) is required for assembly of the N-glycosylation-competent translocon. We report that guanine analog chemical probes identified by high-throughput screening or mutation of the SR-beta guanosine triphosphate binding site cause an N-glycosylation-deficient phenotype. Neither method alters the association of SR-alpha with SR-beta, but both approaches reduce the association of SR-beta with the oligosac-charyltransferase complex. These experiments demonstrate that SR-beta has a previously unrecognized function coordinating endoplasmic reticulum translation with N-glycosylation.
引用
收藏
页数:11
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