Proteolytic activation of human-specific Olduvai domains by the furin protease.
Brain
Furin
Gene expression
Genetic disease
Protease
Journal
International journal of biological macromolecules
ISSN: 1879-0003
Titre abrégé: Int J Biol Macromol
Pays: Netherlands
ID NLM: 7909578
Informations de publication
Date de publication:
15 Apr 2023
15 Apr 2023
Historique:
received:
23
11
2022
accepted:
22
12
2022
pmc-release:
15
04
2024
pubmed:
30
12
2022
medline:
24
3
2023
entrez:
29
12
2022
Statut:
ppublish
Résumé
Olduvai protein domains (formerly DUF1220) show the greatest human-specific increase in copy number of any coding region in the genome and are highly correlated with human brain evolution and cognitive disease. The majority of human copies are found within four NBPF genes organized in a variable number of a tandemly arranged three-domain blocks called Olduvai triplets. Here we show that these human-specific Olduvai domains are posttranslationally processed by the furin protease, with a cleavage site occurring once at each triplet. These findings suggest that all expanded human-specific NBPF genes encode proproteins consisting of many independent Olduvai triplet proteins which are activated by furin processing. The exceptional correlation of Olduvai copy number and brain size taken together with our new furin data, indicates the ultimate target of selection was a rapid increase in dosage of autonomously functioning Olduvai triplet proteins, and that these proteins are the primary active agent underlying Olduvai's role in human brain expansion.
Identifiants
pubmed: 36581038
pii: S0141-8130(22)03181-6
doi: 10.1016/j.ijbiomac.2022.12.260
pmc: PMC10038901
mid: NIHMS1875719
pii:
doi:
Substances chimiques
Furin
EC 3.4.21.75
Peptide Hydrolases
EC 3.4.-
Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
123041Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM130694
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI171827
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kirk C Hansen reports financial support was provided by National Institutes of Health.
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