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.

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 A rapid and affordable screening platform for membrane protein trafficking

BMC Biology ◽  
2015 ◽  
Vol 13 (1) ◽  
Author(s):  
Joshua C. Snyder ◽  
Thomas F. Pack ◽  
Lauren K. Rochelle ◽  
Subhasish K. Chakraborty ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Protein Trafficking ◽  
Membrane Protein Trafficking ◽  
Screening Platform

Ethanol and Membrane Protein Trafficking: Diverse Mechanisms of Ethanol Action

2002 ◽  
Vol 26 (2) ◽  
pp. 287-293 ◽  
Author(s):  
Laura E. Nagy ◽  
M. Raj Lakshman ◽  
Carol A. Casey ◽  
Cynthia F. Bearer
Keyword(s):  
Membrane Protein ◽  
Protein Trafficking ◽  
Membrane Protein Trafficking

scholarly journals Kv2.1 cell surface clusters are insertion platforms for ion channel delivery to the plasma membrane

2012 ◽  
Vol 23 (15) ◽  
pp. 2917-2929 ◽  
Author(s):  
Emily Deutsch ◽  
Aubrey V. Weigel ◽  
Elizabeth J. Akin ◽  
Phil Fox ◽  
Gentry Hansen ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Cell Surface ◽  
Ion Channel ◽  
Protein Trafficking ◽  
Hippocampal Neurons ◽  
Surface Membrane ◽  
Cell Types ◽  
Homogeneous Surface ◽  
Hek Cells ◽  
Membrane Protein Trafficking

Voltage-gated K+ (Kv) channels regulate membrane potential in many cell types. Although the channel surface density and location must be well controlled, little is known about Kv channel delivery and retrieval on the cell surface. The Kv2.1 channel localizes to micron-sized clusters in neurons and transfected human embryonic kidney (HEK) cells, where it is nonconducting. Because Kv2.1 is postulated to be involved in soluble N-ethylmaleimide–sensitive factor attachment protein receptor–mediated membrane fusion, we examined the hypothesis that these surface clusters are specialized platforms involved in membrane protein trafficking. Total internal reflection–based fluorescence recovery after photobleaching studies and quantum dot imaging of single Kv2.1 channels revealed that Kv2.1-containing vesicles deliver cargo at the Kv2.1 surface clusters in both transfected HEK cells and hippocampal neurons. More than 85% of cytoplasmic and recycling Kv2.1 channels was delivered to the cell surface at the cluster perimeter in both cell types. At least 85% of recycling Kv1.4, which, unlike Kv2.1, has a homogeneous surface distribution, is also delivered here. Actin depolymerization resulted in Kv2.1 exocytosis at cluster-free surface membrane. These results indicate that one nonconducting function of Kv2.1 is to form microdomains involved in membrane protein trafficking. This study is the first to identify stable cell surface platforms involved in ion channel trafficking.

scholarly journals Fluorogenic Probing of Membrane Protein Trafficking

2018 ◽  
Vol 29 (6) ◽  
pp. 1823-1828 ◽  
Author(s):  
Chenge Li ◽  
Aurélien Mourton ◽  
Marie-Aude Plamont ◽  
Vanessa Rodrigues ◽  
Isabelle Aujard ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Protein Trafficking ◽  
Membrane Protein Trafficking
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