Spatially conserved motifs in complement control protein domains determine functionality in regulators of complement activation-family proteins.
Amino Acid Motifs
Animals
Cell Adhesion Molecules
/ chemistry
Cnidaria
/ chemistry
Complement Activation
Complement System Proteins
/ chemistry
Conserved Sequence
Humans
Phylogeny
Protein Conformation
Protein Domains
Receptors, Complement 3b
/ chemistry
Structure-Activity Relationship
Viral Proteins
/ chemistry
Biotechnology
Complement cascade
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
2019
2019
Historique:
received:
06
02
2019
accepted:
03
07
2019
entrez:
10
8
2019
pubmed:
10
8
2019
medline:
10
8
2019
Statut:
epublish
Résumé
Regulation of complement activation in the host cells is mediated primarily by the regulators of complement activation (RCA) family proteins that are formed by tandemly repeating complement control protein (CCP) domains. Functional annotation of these proteins, however, is challenging as contiguous CCP domains are found in proteins with varied functions. Here, by employing an in silico approach, we identify five motifs which are conserved spatially in a specific order in the regulatory CCP domains of known RCA proteins. We report that the presence of these motifs in a specific pattern is sufficient to annotate regulatory domains in RCA proteins. We show that incorporation of the lost motif in the fourth long-homologous repeat (LHR-D) in complement receptor 1 regains its regulatory activity. Additionally, the motif pattern also helped annotate human polydom as a complement regulator. Thus, we propose that the motifs identified here are the determinants of functionality in RCA proteins.
Identifiants
pubmed: 31396570
doi: 10.1038/s42003-019-0529-9
pii: 529
pmc: PMC6683126
doi:
Substances chimiques
CR1 protein, human
0
Cell Adhesion Molecules
0
Receptors, Complement 3b
0
SVEP1 protein, human
0
Viral Proteins
0
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
290Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing interests.
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