Positions of cysteine residues reveal local clusters and hidden relationships to Sequons and Transmembrane domains in Human proteins.
Cysteine residues
Disulfide bonds
N-glycosylation
Posttranslational modifications
Protein sequence
Protein structure and function
Sequons
Transmembrane domains
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 10 2024
29 10 2024
Historique:
received:
21
06
2024
accepted:
18
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Membrane proteins often possess critical structural features, such as transmembrane domains (TMs), N-glycosylation, and disulfide bonds (SS bonds), which are essential to their structure and function. Here, we extend the study of the motifs carrying N-glycosylation, i.e. the sequons, and the Cys residues supporting the SS bonds, to the whole human proteome with a particular focus on the Cys positions in human proteins with respect to those of sequons and TMs. As the least abundant amino acid residue in protein sequences, the positions of Cys residues in proteins are not random but rather selected through evolution. We discovered that the frequency of Cys residues in proteins is length dependent, and the frequency of CC gaps formed between adjacent Cys residues can be used as a classifier to distinguish proteins with special structures and functions, such as keratin-associated proteins (KAPs), extracellular proteins with EGF-like domains, and nuclear proteins with zinc finger C2H2 domains. Most importantly, by comparing the positions of Cys residues to those of sequons and TMs, we discovered that these structural features can form dense clusters in highly repeated and mutually exclusive modalities in protein sequences. The evolutionary advantages of such complementarity among the three structural features are discussed, particularly in light of structural dynamics in proteins that are lacking from computational predictions. The discoveries made here highlight the sequence-structure-function axis in biological organisms that can be utilized in future protein engineering toward synthetic biology.
Identifiants
pubmed: 39468182
doi: 10.1038/s41598-024-77056-8
pii: 10.1038/s41598-024-77056-8
doi:
Substances chimiques
Cysteine
K848JZ4886
Membrane Proteins
0
Proteome
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25886Subventions
Organisme : The National Sciences and Engineering Research Council of Canada
ID : RGPIN06073
Organisme : The National Sciences and Engineering Research Council of Canada
ID : RGPIN06073
Informations de copyright
© 2024. The Author(s).
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