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Structure of the human BBSome core complex.

<div class='caption-title'>Architecture of the BBSome.</div>
<div class='caption-title'>Positioning of BBS5 in the BBSome core complex.</div>
<div class='caption-title'>Quality of the model of the BBSome core complex.</div>
Klink BU, Gatsogiannis C, Hofnagel O, Wittinghofer A, Raunser S
OpenAccess logo Elife 9 (2020)
Cited: 39 times
EuropePMC logo PMID: 31951201

Abstract

The BBSome is a heterooctameric protein complex that plays a central role in primary cilia homeostasis. Its malfunction causes the severe ciliopathy Bardet-Biedl syndrome (BBS). The complex acts as a cargo adapter that recognizes signaling proteins such as GPCRs and links them to the intraflagellar transport machinery. The underlying mechanism is poorly understood. Here we present a high-resolution cryo-EM structure of a human heterohexameric core subcomplex of the BBSome. The structure reveals the architecture of the complex in atomic detail. It explains how the subunits interact with each other and how disease-causing mutations hamper this interaction. The complex adopts a conformation that is open for binding to membrane-associated GTPase Arl6 and a large positively charged patch likely strengthens the interaction with the membrane. A prominent negatively charged cleft at the center of the complex is likely involved in binding of positively charged signaling sequences of cargo proteins.

Articles - 6xtb mentioned but not cited (1)

  1. Ubiquitylation of BBSome is required for ciliary assembly and signaling. Chiuso F, Delle Donne R, Giamundo G, Rinaldi L, Borzacchiello D, Moraca F, Intartaglia D, Iannucci R, Senatore E, Lignitto L, Garbi C, Conflitti P, Catalanotti B, Conte I, Feliciello A. EMBO Rep 24 e55571 (2023)


Reviews citing this publication (13)

  1. Intraflagellar transport trains and motors: Insights from structure. Webb S, Mukhopadhyay AG, Roberts AJ. Semin Cell Dev Biol 107 82-90 (2020)
  2. Primary cilia as dynamic and diverse signalling hubs in development and disease. Mill P, Christensen ST, Pedersen LB. Nat Rev Genet 24 421-441 (2023)
  3. Bardet-Biedl Syndrome-Multiple Kaleidoscope Images: Insight into Mechanisms of Genotype-Phenotype Correlations. Florea L, Caba L, Gorduza EV. Genes (Basel) 12 1353 (2021)
  4. Phosphoinositide lipids in primary cilia biology. Conduit SE, Vanhaesebroeck B. Biochem J 477 3541-3565 (2020)
  5. Reciprocal Regulation between Primary Cilia and mTORC1. Lai Y, Jiang Y. Genes (Basel) 11 E711 (2020)
  6. Bardet-Biedl Syndrome: Current Perspectives and Clinical Outlook. Melluso A, Secondulfo F, Capolongo G, Capasso G, Zacchia M. Ther Clin Risk Manag 19 115-132 (2023)
  7. Structural insights into the architecture and assembly of eukaryotic flagella. Petriman NA, Lorentzen E. Microb Cell 7 289-299 (2020)
  8. Cellular and Molecular Mechanisms of Pathogenesis Underlying Inherited Retinal Dystrophies. Manley A, Meshkat BI, Jablonski MM, Hollingsworth TJ. Biomolecules 13 271 (2023)
  9. Organization, functions, and mechanisms of the BBSome in development, ciliopathies, and beyond. Tian X, Zhao H, Zhou J. Elife 12 e87623 (2023)
  10. Ciliary Signalling and Mechanotransduction in the Pathophysiology of Craniosynostosis. Tiberio F, Parolini O, Lattanzi W. Genes (Basel) 12 1073 (2021)
  11. An insight into SARS-CoV-2 structure, pathogenesis, target hunting for drug development and vaccine initiatives. Ghosh A, Kar PK, Gautam A, Gupta R, Singh R, Chakravarti R, Ravichandiran V, Ghosh Dastidar S, Ghosh D, Roy S. RSC Med Chem 13 647-675 (2022)
  12. Structure and Function of Dynein's Non-Catalytic Subunits. Rao L, Gennerich A. Cells 13 330 (2024)
  13. Transport and barrier mechanisms that regulate ciliary compartmentalization and ciliopathies. Moran AL, Louzao-Martinez L, Norris DP, Peters DJM, Blacque OE. Nat Rev Nephrol 20 83-100 (2024)

Articles citing this publication (25)



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