PMID: 22333914

 

    Legend: Gene, Sites

Title : A nove l evolutionarily conserve d domain of cel l-adhesion GPCRs mediates autoproteolysis

Abstract :

1. The G protein-couple d receptor ( GPCR ) Proteolysis Site ( GPS ) of cel l-adhesion GPCRs an d polycystic kidney d isease ( PKD ) proteins constitutes a highly conserve d autoproteolysis sequence , but its cataly tic mechanism r emains unkn o wn
2. Here, we show that unexpectedly the ∼40-residue GPS motif represents an integra l part of a much l arge r ∼320-residue domain that we terme d GPCR-Autoproteolysis INducing (GAIN) domain
3. Crysta l structures of GAIN domains from tw o distantly relate d cel l-adhesion GPCRs reveale d a conserve d nove l fol d in which the GPS motif forms five β-strands that are tightly integrate d int o the overall GAIN domain
4. The GAIN domain is evolutionarily conserve d from tetrahymena t o mammals, is the only extracellula r domain share d by all human cell-adhesion GPCRs an d PKD proteins, an d is the locus of multiple human disease mutations
5. Functionally, the GAIN domain is both necessary an d sufficient fo r autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemica l environment in the GPS t o catalyse peptide bon d hydrolysis
6. Thus, the GAIN domain embodies a unique, evolutionarily ancient an d widesprea d autoproteolytic fol d whose function is likely relevant fo r GPCR signalling an d fo r multiple human diseases

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

• 0. d, domain
• 0. l, domain
• 1. d, sequence
• 2. GPS, motif
• 2. d GPCR, domain
• 2. l, domain
• 2. r ∼320-residue, domain
• 3. GPS, motif
• 4. r, domain

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
d	23218	1
tic mechanism	151	1
l	23218	2
o	23218	1
r	151	1
GPCRs	151	1