6TS2

Truncated version of Chaetomium thermophilum UDP-Glucose Glucosyl Transferase (UGGT) lacking domain TRXL2 (417-650).

Summary for 6TS2

• Entry DOI: 10.2210/pdb6ts2/pdb
• Related: 3wzs 3wzt 5mu2 5mzo 5n2j 5nV4 6fsn 6trf 6trt
• Descriptor: UDP-glucose-glycoprotein glucosyltransferase-like protein,UDP-glucose-glycoprotein glucosyltransferase-like protein, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: endoplasmic reticulum, glycoprotein folding, erqc, uggt, truncation, deletion, thioredoxin-like domain, protein binding
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719); More
• Total number of polymer chains: 4
• Total formula weight: 575330.15

Authors

Roversi, P.,Zitzmann, N. (deposition date: 2019-12-19, release date: 2020-01-08, Last modification date: 2024-11-20)

Primary citation

Modenutti, C.P.,Blanco Capurro, J.I.,Ibba, R.,Alonzi, D.S.,Song, M.N.,Vasiljevic, S.,Kumar, A.,Chandran, A.V.,Tax, G.,Marti, L.,Hill, J.C.,Lia, A.,Hensen, M.,Waksman, T.,Rushton, J.,Rubichi, S.,Santino, A.,Marti, M.A.,Zitzmann, N.,Roversi, P.
Clamping, bending, and twisting inter-domain motions in the misfold-recognizing portion of UDP-glucose: Glycoprotein glucosyltransferase.
Structure, 29:357-, 2021

PubMed Abstract: UDP-glucose:glycoprotein glucosyltransferase (UGGT) flags misfolded glycoproteins for ER retention. We report crystal structures of full-length Chaetomium thermophilum UGGT (CtUGGT), two CtUGGT double-cysteine mutants, and its TRXL2 domain truncation (CtUGGT-ΔTRXL2). CtUGGT molecular dynamics (MD) simulations capture extended conformations and reveal clamping, bending, and twisting inter-domain movements. We name "Parodi limit" the maximum distance on the same glycoprotein between a site of misfolding and an N-linked glycan that can be reglucosylated by monomeric UGGT in vitro, in response to recognition of misfold at that site. Based on the MD simulations, we estimate the Parodi limit as around 70-80 Å. Frequency distributions of distances between glycoprotein residues and their closest N-linked glycosylation sites in glycoprotein crystal structures suggests relevance of the Parodi limit to UGGT activity in vivo. Our data support a "one-size-fits-all adjustable spanner" UGGT substrate recognition model, with an essential role for the UGGT TRXL2 domain.

PubMed: 33352114
DOI: 10.1016/j.str.2020.11.017

Experimental method

X-RAY DIFFRACTION (5.74 Å)