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Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

The GIPC family adaptor proteins mediate endocytosis by tethering cargo proteins to the myosin VI motor. The structural mechanisms for the GIPC/cargo and GIPC/myosin VI interactions remained unclear. PlexinD1, a transmembrane receptor that regulates neuronal and cardiovascular development, is a cargo of GIPCs. GIPC-mediated endocytic trafficking regulates PlexinD1 signaling. Here, we unravel the mechanisms of the interactions among PlexinD1, GIPCs and myosin VI by a series of crystal structures of these proteins in apo or bound states. GIPC1 forms a domain-swapped dimer in an autoinhibited conformation that hinders binding of both PlexinD1 and myosin VI. PlexinD1 binding to GIPC1 releases the autoinhibition, promoting its interaction with myosin VI. GIPCs and myosin VI interact through two distinct interfaces and form an open-ended alternating array. Our data support that this alternating array underlies the oligomerization of the GIPC/Myosin VI complexes in solution and cells.

Elife. 2017 May 24;6. pii: e27322.
doi: 10.7554/eLife.27322.

 

© 2017 eLife Sciences Publications Ltd.

  Shang G, Brautigam CA, Chen R, Lu D, Torres-Vázquez J, Zhang X.

Further Back:

A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants
A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants

 

Sci Transl Med. 2017 May 3;9(388).
pii: eaaj1928. doi: 10.1126/scitranslmed.aaj1928.

 

Structure of a symmetric photosynthetic reaction center-photosystem

Structure of a symmetric photosynthetic reaction center-photosystem

 

Science. 2017 Sep 8;357(6355):1021-1025.
doi: 10.1126/science.aan5611. Epub 2017 Jul 27.

And Even Further Back:

Sidebar_2017_01
2017

 

Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation.

 

A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants.

 

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture.

 

Structural basis for human respiratory syncytial virus NS1-mediated modulation of host responses.

 

Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis.

 

A novel signal transduction protein: Combination of solute binding and tandem PAS-like sensor domains in one polypeptide chains.

 

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.

 

Inhibition of RAS function through targeting an allosteric regulatory site.

 

Structural Basis for Ligand Binding to the Guanidine-I Riboswitchs.

Sidebar_2016_01
2016

 

NPAS1-ARNT and NPAS3-ARNT crystal structures implicate the bHLH-PAS family as multi-ligand binding transcription factors.

 

Bile salt receptor complex activates a pathogenic type III secretion system.

 

Crystal Structure of the FERM-SH2 Module of Human Jak2.

 

Structural Studies of Medicago truncatula Histidinol Phosphate Phosphatase from Inositol Monophosphatase Superfamily Reveal Details of Penultimate Step of Histidine Biosynthesis in Plant.

 

Crystal structure of the human sterol transporter ABCG5/ABCG8.

 

Structural basis of cohesin cleavage by separase.

 

Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana.

 

Structural and molecular basis for Ebola virus neutralization by protective human antibodies.

Sidebar_2015_01
2015

 

A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria

 

Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2

 

A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism

 

EsxB, a secreted protein from Bacillus anthracis forms two distinct helical bundles

 

Functional Diversity of Haloacid Dehalogenase Superfamily Phosphatases from Saccharomyces cerevisiae

 

An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA Synthesis by Modulating Nucleoprotein-RNA Interactions

 

Crystal structures of alkylperoxo and anhydride intermediates in an intradiol ring-cleaving dioxygenase

 

Sidebar_2017_01
2017

 

Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex.

 

Structure of a symmetric photosynthetic reaction center-photosystem.

 

A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease.

 

The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily.

 

Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition.

 

A Sensitive in Vitro High-Throughput Screen To Identify Pan-filoviral Replication Inhibitors Targeting the VP35−NP Interface.

 

Structure of the active form of human origin recognition complex and its ATPase motor module.

 

Non-classical transpeptidases yield insight into new antibacterials.

Sidebar_2016_02
2016

 

Crystal structures of the human elongation factor eEFSec suggest a non-canonical mechanism for selenocysteine incorporation.

 

Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase.

 

Phosphorylation of spore coat proteins by a family of atypical protein kinases.

 

The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA.

 

The Vaccinia Virus H3 Envelope Protein, a Major Target of Neutralizing Antibodies, Exhibits a Glycosyltransferase Fold and Binds UDP-Glucose.

 

Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway.

 

Molecular mechanism of respiratory syncytial virus fusion inhibitors.

Sidebar_2015_02
2015

 

Crystal Structure of the Zorbamycin-Binding Protein ZbmA, the Primary Self-Resistance Element in Streptomyces flavoviridis ATCC21892

 

Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion

 

Sperm Lysozyme-Like Protein 1 (SLLP1), an intra-acrosomal oolemmal-binding sperm protein, reveals filamentous organization in protein crystal form

 

Structural integration in hypoxia-inducible factors

 

New aminopeptidase from microbial dark matter archaeon

 

A Novel Cofactor-binding Mode in Bacterial IMP Dehydrogenases Explains Inhibitor Selectivity

 

Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phos. STAT1