Assembly of higher-order SMN oligomers is essential for metazoan viability and requires an exposed structural motif present in the YG zipper dimer.
Amino Acid Motifs
Amino Acid Sequence
Animals
Conserved Sequence
Dimerization
Drosophila Proteins
/ chemistry
Drosophila melanogaster
/ physiology
Humans
Locomotion
Models, Molecular
Mutation
Point Mutation
Protein Domains
Protein Multimerization
SMN Complex Proteins
/ chemistry
Schizosaccharomyces pombe Proteins
/ chemistry
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
21 07 2021
21 07 2021
Historique:
accepted:
03
06
2021
received:
18
05
2021
pubmed:
29
6
2021
medline:
10
8
2021
entrez:
28
6
2021
Statut:
ppublish
Résumé
Protein oligomerization is one mechanism by which homogenous solutions can separate into distinct liquid phases, enabling assembly of membraneless organelles. Survival Motor Neuron (SMN) is the eponymous component of a large macromolecular complex that chaperones biogenesis of eukaryotic ribonucleoproteins and localizes to distinct membraneless organelles in both the nucleus and cytoplasm. SMN forms the oligomeric core of this complex, and missense mutations within its YG box domain are known to cause Spinal Muscular Atrophy (SMA). The SMN YG box utilizes a unique variant of the glycine zipper motif to form dimers, but the mechanism of higher-order oligomerization remains unknown. Here, we use a combination of molecular genetic, phylogenetic, biophysical, biochemical and computational approaches to show that formation of higher-order SMN oligomers depends on a set of YG box residues that are not involved in dimerization. Mutation of key residues within this new structural motif restricts assembly of SMN to dimers and causes locomotor dysfunction and viability defects in animal models.
Identifiants
pubmed: 34181727
pii: 6310796
doi: 10.1093/nar/gkab508
pmc: PMC8287954
doi:
Substances chimiques
Drosophila Proteins
0
SMN Complex Proteins
0
Schizosaccharomyces pombe Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
7644-7664Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM136435
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM124169
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108751
Pays : United States
Organisme : NIH HHS
ID : S10 OD030413
Pays : United States
Organisme : NIH HHS
ID : S10 OD018483
Pays : United States
Organisme : NIGMS NIH HHS
ID : K12 GM000678
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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