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Structure and activation mechanism of the BBSome membrane protein trafficking complex.

<div class='caption-title'>Structure of the mammalian BBSome.</div>
<div class='caption-title'>Cryo-EM data processing.</div>
<div class='caption-title'>Data quality.</div>
Singh SK, Gui M, Koh F, Yip MC, Brown A
OpenAccess logo Elife 9 (2020)
Cited: 33 times
EuropePMC logo PMID: 31939736

Abstract

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.

Articles - 6vbu mentioned but not cited (3)

  1. Structure and activation mechanism of the BBSome membrane protein trafficking complex. Singh SK, Gui M, Koh F, Yip MC, Brown A. Elife 9 e53322 (2020)
  2. 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)
  3. WGS Revealed Novel BBS5 Pathogenic Variants, Missed by WES, Causing Ciliary Structure and Function Defects. Karam A, Delvallée C, Estrada-Cuzcano A, Geoffroy V, Lamouche JB, Leuvrey AS, Nourisson E, Tarabeux J, Stoetzel C, Scheidecker S, Porter LF, Génin E, Redon R, Sandron F, Boland A, Deleuze JF, Le May N, Dollfus H, Muller J. Int J Mol Sci 24 8729 (2023)


Reviews citing this publication (10)

  1. Intraflagellar transport trains and motors: Insights from structure. Webb S, Mukhopadhyay AG, Roberts AJ. Semin Cell Dev Biol 107 82-90 (2020)
  2. Bardet-Biedl Syndrome-Multiple Kaleidoscope Images: Insight into Mechanisms of Genotype-Phenotype Correlations. Florea L, Caba L, Gorduza EV. Genes (Basel) 12 1353 (2021)
  3. Phosphoinositide lipids in primary cilia biology. Conduit SE, Vanhaesebroeck B. Biochem J 477 3541-3565 (2020)
  4. 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)
  5. The Enigmatic Role of Lipids in Cilia Signaling. Nechipurenko IV. Front Cell Dev Biol 8 777 (2020)
  6. Cargo adapters expand the transport range of intraflagellar transport. Lechtreck K. J Cell Sci 135 jcs260408 (2022)
  7. Structural insights into the architecture and assembly of eukaryotic flagella. Petriman NA, Lorentzen E. Microb Cell 7 289-299 (2020)
  8. Using Paramecium as a Model for Ciliopathies. Valentine M, Van Houten J. Genes (Basel) 12 1493 (2021)
  9. Organization, functions, and mechanisms of the BBSome in development, ciliopathies, and beyond. Tian X, Zhao H, Zhou J. Elife 12 e87623 (2023)
  10. Genetic dissection of non-syndromic retinitis pigmentosa. Bhardwaj A, Yadav A, Yadav M, Tanwar M. Indian J Ophthalmol 70 2355-2385 (2022)

Articles citing this publication (20)



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