Clamping, bending, and twisting inter-domain motions in the misfold-recognizing portion of UDP-glucose: Glycoprotein glucosyltransferase

被引：195

作者：

Modenutti, Carlos P. ^{[1
,2
]}

Blanco Capurro, Juan, I ^{[1
,2
]}

Ibba, Roberta ^{[3
,4
]}

Alonzi, Dominic S. ^{[3
]}

Song, Mauro N. ^{[1
,2
]}

Vasiljevic, Snezana ^{[3
]}

Kumar, Abhinav ^{[3
]}

Chandran, Anu, V ^{[3
]}

Tax, Gabor ^{[5
]}

Marti, Lucia ^{[6
]}

Hill, Johan C. ^{[3
]}

Lia, Andrea ^{[3
,5
,6
]}

Hensen, Mario ^{[3
]}

Waksman, Thomas ^{[3
]}

Rushton, Jonathan ^{[3
]}

Rubichi, Simone ^{[3
,6
]}

Santino, Angelo ^{[6
]}

Marti, Marcelo A. ^{[1
,2
]}

Zitzmann, Nicole ^{[3
]}

Roversi, Pietro ^{[3
,5
]}

机构：

[1] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Biol, Ciudad Univ,Pab 2,CE1428EHA, Buenos Aires, DF, Argentina

[2] Consejo Nacl Invest Cient & Tecn, Inst Quim Biol, Fac Ciencias Exactas & Nat IQUIBICEN, Ciudad Univ,Pab 2,CE1428EHA, Buenos Aires, DF, Argentina

[3] Univ Oxford, Oxford Glycobiol Inst, Dept Biochem, Oxford OX1 3QU, England

[4] Univ Sassari, Dipartimento Chim & Farm, Via Muroni 23A, I-07100 Sassari, SS, Italy

[5] Univ Leicester, Leicester Inst Struct & Chem Biol, Dept Mol & Cell Biol, Henry Wellcome Bldg,Lancaster Rd, Leicester LE1 7RH, Leics, England

[6] CNR, Inst Sci Food Prod, Unit Lecce, Via Monteroni, I-73100 Lecce, Italy

来源：

STRUCTURE | 2021年 / 29卷 / 04期

基金：

英国惠康基金;

关键词：

ENDOPLASMIC-RETICULUM; QUALITY-CONTROL; RESIDENT GLYCOPROTEIN; MASS-SPECTROMETRY; PROTEIN; REFINEMENT; SYSTEM; VISUALIZATION; RECOGNITION; EXPRESSION;

D O I：

10.1016/j.str.2020.11.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-Delta TRXL2). 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 bymonomeric 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 angstrom. 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.

引用

页码：357 / +

页数：23

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