Membrane Proteome: GPCR Substrate Recognition and Functional Selectivity

2013 ◽  
Author(s):  
Michelle Montoya
Keyword(s):  
Substrate Recognition ◽  
Functional Selectivity ◽  
Membrane Proteome

scholarly journals Structure and activation mechanism of the BBSome membrane-protein trafficking complex

2019 ◽  
Author(s):  
Sandeep Singh ◽  
Miao Gui ◽  
Fujiet Koh ◽  
Matthew C.J. Yip ◽  
Alan Brown
Keyword(s):  
Membrane Protein ◽  
Protein Trafficking ◽  
Substrate Recognition ◽  
Activation Mechanism ◽  
Electron Cryomicroscopy ◽  
Membrane Proteome ◽  
Central Cavity ◽  
Structural Mapping ◽  
Bardet Biedl Syndrome ◽  
Membrane Protein Trafficking

AbstractBardet-Biedl syndrome (BBS) is an incurable ciliopathy caused by the failure to correctly establish or maintain cilia-dependent signaling pathways. Eight proteins associated with BBS assemble into the BBSome, a master regulator of the ciliary membrane proteome. We report the electron cryomicroscopy (cryo-EM) structures of the native bovine BBSome in inactive and active states at 3.1 and 3.5 Å resolution, respectively. In the active state, the BBSome is bound to an Arf-family GTPase (ARL6/BBS3) that recruits the BBSome to ciliary membranes. ARL6 recognizes a composite binding site formed by BBS1 and BBS7 that is occluded in the inactive state. Activation requires an unexpected swiveling of the β-propeller domain of BBS1, the key subunit implicated in substrate recognition, which widens a central cavity of the BBSome. Structural mapping of disease-causing mutations suggests that pathogenesis predominantly results from disruption of autoinhibition and activation.

scholarly journals Structure and activation mechanism of the BBSome membrane protein trafficking complex

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Sandeep K Singh ◽  
Miao Gui ◽  
Fujiet Koh ◽  
Matthew CJ Yip ◽  
Alan Brown
Keyword(s):  
Membrane Protein ◽  
Protein Trafficking ◽  
Substrate Recognition ◽  
Activation Mechanism ◽  
Electron Cryomicroscopy ◽  
Membrane Proteome ◽  
Central Cavity ◽  
Structural Mapping ◽  
Bardet Biedl Syndrome ◽  
Membrane Protein Trafficking

Bardet-Biedl syndrome (BBS) is a currently incurable ciliopathy caused by the failure to correctly establish or maintain cilia-dependent signaling pathways. Eight proteins associated with BBS assemble into the BBSome, a key regulator of the ciliary membrane proteome. We report the electron cryomicroscopy (cryo-EM) structures of the native bovine BBSome in inactive and active states at 3.1 and 3.5 Å resolution, respectively. In the active state, the BBSome is bound to an Arf-family GTPase (ARL6/BBS3) that recruits the BBSome to ciliary membranes. ARL6 recognizes a composite binding site formed by BBS1 and BBS7 that is occluded in the inactive state. Activation requires an unexpected swiveling of the β-propeller domain of BBS1, the subunit most frequently implicated in substrate recognition, which widens a central cavity of the BBSome. Structural mapping of disease-causing mutations suggests that pathogenesis results from folding defects and the disruption of autoinhibition and activation.

Substrate Recognition by Vitamin K-Dependent Carboxylase

1987 ◽  
Vol 57 (01) ◽  
pp. 017-019 ◽  
Author(s):  
Magda M W Ulrich ◽  
Berry A M Soute ◽  
L Johan M van Haarlem ◽  
Cees Vermeer
Keyword(s):  
Amino Acid ◽  
Vitamin K ◽  
Substrate Recognition ◽  
Bovine Liver ◽  
Amino Acid Residues

SummaryDecarboxylated osteocalcins were prepared and purified from bovine, chicken, human and monkey bones and assayed for their ability to serve as a substrate for vitamin K-dependent carboxylase from bovine liver. Substantial differences were observed, especially between bovine and monkey d-osteocalcin. Since these substrates differ only in their amino acid residues 3 and 4, it seems that these residues play a role in the recognition of a substrate by hepatic carboxylase.

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