6GWJ

Human OSGEP / LAGE3 / GON7 complex

Summary for 6GWJ

• Entry DOI: 10.2210/pdb6gwj/pdb
• Descriptor: EKC/KEOPS complex subunit LAGE3, EKC/KEOPS complex subunit GON7, Probable tRNA N6-adenosine threonylcarbamoyltransferase, ... (8 entities in total)
• Functional Keywords: trna, t6a modification, rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 63915.47

Authors

Missoury, S.,Liger, D.,Durand, D.,Collinet, B.,Tilbeurgh, V.H. (deposition date: 2018-06-25, release date: 2019-07-03, Last modification date: 2024-05-15)

Primary citation

Arrondel, C.,Missoury, S.,Snoek, R.,Patat, J.,Menara, G.,Collinet, B.,Liger, D.,Durand, D.,Gribouval, O.,Boyer, O.,Buscara, L.,Martin, G.,Machuca, E.,Nevo, F.,Lescop, E.,Braun, D.A.,Boschat, A.C.,Sanquer, S.,Guerrera, I.C.,Revy, P.,Parisot, M.,Masson, C.,Boddaert, N.,Charbit, M.,Decramer, S.,Novo, R.,Macher, M.A.,Ranchin, B.,Bacchetta, J.,Laurent, A.,Collardeau-Frachon, S.,van Eerde, A.M.,Hildebrandt, F.,Magen, D.,Antignac, C.,van Tilbeurgh, H.,Mollet, G.
Defects in t 6 A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome.
Nat Commun, 10:3967-3967, 2019

PubMed Abstract: N-threonyl-carbamoylation of adenosine 37 of ANN-type tRNAs (tA) is a universal modification essential for translational accuracy and efficiency. The tA pathway uses two sequentially acting enzymes, YRDC and OSGEP, the latter being a subunit of the multiprotein KEOPS complex. We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease. The crystal structure of the GON7/LAGE3/OSGEP subcomplex shows that the intrinsically disordered GON7 protein becomes partially structured upon binding to LAGE3. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex.

PubMed: 31481669
DOI: 10.1038/s41467-019-11951-x

Experimental method

X-RAY DIFFRACTION (1.95 Å)