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Structural basis for membrane targeting of the BBSome by ARL6.

<div class='caption-title'>Structure of Chlamydomonas reinhardtii ARL6ΔN-GTP-BBS1 complex</div>
<div class='caption-title'>Structural basis of the ARL6-BBS1 interaction</div>
<div class='caption-title'>Disruption of the ARL6–BBS1 interface prevents recruitment of the BBSome to cilia</div>
Mourão A, Nager AR, Nachury MV, Lorentzen E
OpenAccess logo Nat Struct Mol Biol 21 1035-41 (2014)
Related entries: 4v0k, 4v0l, 4v0n, 4v0o

Cited: 53 times
EuropePMC logo PMID: 25402481

Abstract

The BBSome is a coat-like ciliary trafficking complex composed of proteins mutated in Bardet-Biedl syndrome (BBS). A critical step in BBSome-mediated sorting is recruitment of the BBSome to membranes by the GTP-bound Arf-like GTPase ARL6. We have determined crystal structures of Chlamydomonas reinhardtii ARL6-GDP, ARL6-GTP and the ARL6-GTP-BBS1 complex. The structures demonstrate how ARL6-GTP binds the BBS1 β-propeller at blades 1 and 7 and explain why GTP- but not GDP-bound ARL6 can recruit the BBSome to membranes. Single point mutations in the ARL6-GTP-BBS1 interface abolish the interaction of ARL6 with the BBSome and prevent the import of BBSomes into cilia. Furthermore, we show that BBS1 with the M390R mutation, responsible for 30% of all reported BBS disease cases, fails to interact with ARL6-GTP, thus providing a molecular rationale for patient pathologies.

Articles - 4v0m mentioned but not cited (4)

  1. Structural basis for membrane targeting of the BBSome by ARL6. Mourão A, Nager AR, Nachury MV, Lorentzen E. Nat Struct Mol Biol 21 1035-1041 (2014)
  2. The Molecular Architecture of Native BBSome Obtained by an Integrated Structural Approach. Chou HT, Apelt L, Farrell DP, White SR, Woodsmith J, Svetlov V, Goldstein JS, Nager AR, Li Z, Muller J, Dollfus H, Nudler E, Stelzl U, DiMaio F, Nachury MV, Walz T. Structure 27 1384-1394.e4 (2019)
  3. Defining the Domain Arrangement of the Mammalian Target of Rapamycin Complex Component Rictor Protein. Zhou P, Zhang N, Nussinov R, Ma B. J Comput Biol 22 876-886 (2015)
  4. Structural Characterization of Bardet-Biedl Syndrome 9 Protein (BBS9). Knockenhauer KE, Schwartz TU. J Biol Chem 290 19569-19583 (2015)


Reviews citing this publication (17)

  1. IFT-Cargo Interactions and Protein Transport in Cilia. Lechtreck KF. Trends Biochem Sci 40 765-778 (2015)
  2. The Intraflagellar Transport Machinery. Taschner M, Taschner M, Lorentzen E. Cold Spring Harb Perspect Biol 8 a028092 (2016)
  3. Ins and outs of GPCR signaling in primary cilia. Schou KB, Pedersen LB, Christensen ST. EMBO Rep 16 1099-1113 (2015)
  4. How the Ciliary Membrane Is Organized Inside-Out to Communicate Outside-In. Garcia G, Raleigh DR, Reiter JF. Curr Biol 28 R421-R434 (2018)
  5. Trafficking of ciliary membrane proteins by the intraflagellar transport/BBSome machinery. Wingfield JL, Lechtreck KF, Lorentzen E. Essays Biochem 62 753-763 (2018)
  6. Cilia and Obesity. Vaisse C, Reiter JF, Berbari NF. Cold Spring Harb Perspect Biol 9 a028217 (2017)
  7. The intraflagellar transport machinery in ciliary signaling. Mourão A, Christensen ST, Lorentzen E. Curr Opin Struct Biol 41 98-108 (2016)
  8. Bardet-Biedl syndrome: Is it only cilia dysfunction? Novas R, Cardenas-Rodriguez M, Irigoín F, Badano JL. FEBS Lett 589 3479-3491 (2015)
  9. Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis. Paczkowski JE, Richardson BC, Fromme JC. Trends Cell Biol 25 408-416 (2015)
  10. Allosteric regulation of Arf GTPases and their GEFs at the membrane interface. Nawrotek A, Zeghouf M, Cherfils J. Small GTPases 7 283-296 (2016)
  11. Regulation of ciliary membrane protein trafficking and signalling by kinesin motor proteins. Morthorst SK, Christensen ST, Pedersen LB. FEBS J 285 4535-4564 (2018)
  12. Cargo adapters expand the transport range of intraflagellar transport. Lechtreck K. J Cell Sci 135 jcs260408 (2022)
  13. 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)
  14. Novel topography of the Rab11-effector interaction network within a ciliary membrane targeting complex. Vetter M, Wang J, Lorentzen E, Deretic D. Small GTPases 6 165-173 (2015)
  15. Organization, functions, and mechanisms of the BBSome in development, ciliopathies, and beyond. Tian X, Zhao H, Zhou J. Elife 12 e87623 (2023)
  16. Maintaining protein composition in cilia. Stephen LA, Elmaghloob Y, Ismail S. Biol Chem 399 1-11 (2017)
  17. Appearing and disappearing acts of cilia. Arora S, Rana M, Sachdev A, D'Souza JS. J Biosci 48 8 (2023)

Articles citing this publication (32)



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