6R6G

Structure of XBP1u-paused ribosome nascent chain complex with SRP.

This is a non-PDB format compatible entry.

Summary for 6R6G

• Entry DOI: 10.2210/pdb6r6g/pdb
• Related: 6R5Q
• EMDB information: 4729 4735
• Descriptor: eS31, uS14, uL2, ... (94 entities in total)
• Functional Keywords: translational pausing, xbp1, upr, cotranslational targeting, srp., ribosome
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 92
• Total formula weight: 3366388.66

Authors

Shanmuganathan, V.,Cheng, J.,Braunger, K.,Berninghausen, O.,Beatrix, B.,Beckmann, R. (deposition date: 2019-03-27, release date: 2019-07-10, Last modification date: 2019-10-30)

Primary citation

Shanmuganathan, V.,Schiller, N.,Magoulopoulou, A.,Cheng, J.,Braunger, K.,Cymer, F.,Berninghausen, O.,Beatrix, B.,Kohno, K.,Heijne, G.V.,Beckmann, R.
Structural and mutational analysis of the ribosome-arresting human XBP1u.
Elife, 8:-, 2019

PubMed Abstract: XBP1u, a central component of the unfolded protein response (UPR), is a mammalian protein containing a functionally critical translational arrest peptide (AP). Here, we present a 3 Å cryo-EM structure of the stalled human XBP1u AP. It forms a unique turn in the ribosomal exit tunnel proximal to the peptidyl transferase center where it causes a subtle distortion, thereby explaining the temporary translational arrest induced by XBP1u. During ribosomal pausing the hydrophobic region 2 (HR2) of XBP1u is recognized by SRP, but fails to efficiently gate the Sec61 translocon. An exhaustive mutagenesis scan of the XBP1u AP revealed that only 8 out of 20 mutagenized positions are optimal; in the remaining 12 positions, we identify 55 different mutations increase the level of translational arrest. Thus, the wildtype XBP1u AP induces only an intermediate level of translational arrest, allowing efficient targeting by SRP without activating the Sec61 channel.

PubMed: 31246176
DOI: 10.7554/eLife.46267

Experimental method

ELECTRON MICROSCOPY (3.7 Å)