Faculty Opinions recommendation of Structural basis for recruitment and activation of the AP-1 clathrin adaptor complex by Arf1.

2013 ◽  
Author(s):  
Karin M Reinisch ◽  
Florian Horenkamp
Keyword(s):  
Structural Basis ◽  
Clathrin Adaptor

scholarly journals Structural basis for tetherin antagonism as a barrier to zoonotic lentiviral transmission

2019 ◽  
Author(s):  
Cosmo Z. Buffalo ◽  
Christina M. Stürzel ◽  
Elena Heusinger ◽  
Dorota Kmiec ◽  
Frank Kirchhoff ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Binding Site ◽  
Host Defense ◽  
Structural Basis ◽  
Viral Infectivity ◽  
Mhc I ◽  
Human Tetherin ◽  
Clathrin Adaptor ◽  
Α Helix ◽  
Tetherin Antagonism

AbstractTetherin is a host defense that physically prevents escape of virions from the plasma membrane. Human tetherin lacks the motif DIWK antagonized by SIV, the antecedent of HIV. Here, we reconstituted the AP-2 clathrin adaptor complex with a simian tetherin and SIV Nef and determined its structure by cryo-EM. Nef refolds the first α-helix of the β2 subunit of AP-2 to a β hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of MHC-I, CD3, and CD4, but overlaps the site for SERINC5 restricting viral infectivity. The structure explains the dependence of SIVs on the host tetherin DIWK sequence and the consequent barrier to human transmission.

scholarly journals Structural Basis for Recruitment and Activation of the AP-1 Clathrin Adaptor Complex by Arf1

Cell ◽  
2013 ◽  
Vol 152 (4) ◽  
pp. 755-767 ◽  
Author(s):  
Xuefeng Ren ◽  
Ginny G. Farías ◽  
Bertram J. Canagarajah ◽  
Juan S. Bonifacino ◽  
James H. Hurley
Keyword(s):  
Structural Basis ◽  
Clathrin Adaptor

scholarly journals Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Xiaofei Jia ◽  
Erin Weber ◽  
Andrey Tokarev ◽  
Mary Lewinski ◽  
Maryan Rizk ◽  
...  
Keyword(s):  
Cell Surface ◽  
Membrane Trafficking ◽  
Protein Complex ◽  
Adaptor Protein ◽  
Structural Basis ◽  
Host Proteins ◽  
Viral Protein U ◽  
Sorting Motif ◽  
Clathrin Adaptor ◽  
Hiv 1

BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins.

scholarly journals How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Xuefeng Ren ◽  
Sang Yoon Park ◽  
Juan S Bonifacino ◽  
James H Hurley
Keyword(s):  
Crystal Structure ◽  
Cell Surface ◽  
Binding Site ◽  
Indirect Interactions ◽  
Structural Basis ◽  
Clathrin Adaptor ◽  
Central Loop ◽  
Hiv 1

The Nef protein of HIV-1 downregulates the cell surface co-receptor CD4 by hijacking the clathrin adaptor complex AP-2. The structural basis for the hijacking of AP-2 by Nef is revealed by a 2.9 Å crystal structure of Nef bound to the α and σ2 subunits of AP-2. Nef binds to AP-2 via its central loop (residues 149–179) and its core. The determinants for Nef binding include residues that directly contact AP-2 and others that stabilize the binding-competent conformation of the central loop. Residues involved in both direct and indirect interactions are required for the binding of Nef to AP-2 and for downregulation of CD4. These results lead to a model for the docking of the full AP-2 tetramer to membranes as bound to Nef, such that the cytosolic tail of CD4 is situated to interact with its binding site on Nef.

scholarly journals Structural basis of GABARAP-mediated GABAA receptor trafficking and functions on GABAergic synaptic transmission

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jin Ye ◽  
Guichang Zou ◽  
Ruichi Zhu ◽  
Chao Kong ◽  
Chenjian Miao ◽  
...  
Keyword(s):  
Complex Formation ◽  
Molecular Mechanisms ◽  
Adaptor Protein ◽  
Structural Basis ◽  
Synaptic Localization ◽  
Central Nervous System Dysfunction ◽  
Trafficking Pathway ◽  
The Central Nervous System ◽  
Clathrin Adaptor ◽  
The Stability

AbstractGABAA receptors (GABAARs) are the primary fast inhibitory ion channels in the central nervous system. Dysfunction of trafficking and localization of GABAARs to cell membranes is clinically associated with severe psychiatric disorders in humans. The GABARAP protein is known to support the stability of GABAARs in synapses, but the underlying molecular mechanisms remain to be elucidated. Here, we show that GABARAP/GABARAPL1 directly binds to a previously unappreciated region in the γ2 subunit of GABAAR. We demonstrate that GABARAP functions to stabilize GABAARs via promoting its trafficking pathway instead of blocking receptor endocytosis. The GABARAPL1–γ2-GABAAR crystal structure reveals the mechanisms underlying the complex formation. We provide evidence showing that phosphorylation of γ2-GABAAR differentially modulate the receptor’s binding to GABARAP and the clathrin adaptor protein AP2. Finally, we demonstrate that GABAergic synaptic currents are reduced upon specific blockage of the GABARAP–GABAAR complex formation. Collectively, our results reveal that GABARAP/GABARAPL1, but not other members of the Atg8 family proteins, specifically regulates synaptic localization of GABAARs via modulating the trafficking of the receptor.

scholarly journals Author response: Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1

2014 ◽  
Author(s):  
Xiaofei Jia ◽  
Erin Weber ◽  
Andrey Tokarev ◽  
Mary Lewinski ◽  
Maryan Rizk ◽  
...  
Keyword(s):  
Protein Complex ◽  
Adaptor Protein ◽  
Author Response ◽  
Structural Basis ◽  
Clathrin Adaptor ◽  
Hiv 1

Organization of tight junctions in the choroid plexus epithelium

1978 ◽  
Vol 36 (2) ◽  
pp. 336-337
Author(s):  
B. Van Deurs ◽  
J. K. Koehler
Keyword(s):  
Choroid Plexus ◽  
Present Report ◽  
Freeze Fracture ◽  
Barrier Properties ◽  
Cell Junctions ◽  
Structural Basis ◽  
Apical Surface ◽  
Choroid Plexus Epithelium ◽  
Solid Nitrogen ◽  
Special Composition

The choroid plexus epithelium constitutes a blood-cerebrospinal fluid (CSF) barrier, and is involved in regulation of the special composition of the CSF. The epithelium is provided with an ouabain-sensitive Na/K-pump located at the apical surface, actively pumping ions into the CSF. The choroid plexus epithelium has been described as “leaky” with a low transepithelial resistance, and a passive transepithelial flux following a paracellular route (intercellular spaces and cell junctions) also takes place. The present report describes the structural basis for these “barrier” properties of the choroid plexus epithelium as revealed by freeze fracture.Choroid plexus from the lateral, third and fourth ventricles of rats were used. The tissue was fixed in glutaraldehyde and stored in 30% glycerol. Freezing was performed either in liquid nitrogen-cooled Freon 22, or directly in a mixture of liquid and solid nitrogen prepared in a special vacuum chamber. The latter method was always used, and considered necessary, when preparations of complementary (double) replicas were made.

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