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Elucidation of Rab27 recruitment by its effectors: structure of Rab27a bound to Exophilin4/Slp2-a.

Chavas LM, Ihara K, Kawasaki M, Torii S, Uejima T, Kato R, Izumi T, Wakatsuki S
Structure 16 1468-77 (2008)
Cited: 45 times
EuropePMC logo PMID: 18940603

Abstract

Rab GTPases coordinate vesicular trafficking within eukaryotic cells by collaborating with a set of effector proteins. Rab27a regulates numerous exocytotic pathways, and its dysfunction causes the Griscelli syndrome human immunodeficiency. Exophilin4/Slp2-a localizes on phosphatidylserine-enriched plasma membrane, and its N-terminal Rab27-binding domain (RBD27) specifically recognizes Rab27 on the surfaces of melanosomes and secretory granules prior to docking and fusion. To characterize the selective binding of Rab27 to 11 various effectors, we have determined the 1.8 A resolution structure of Rab27a in complex with Exophilin4 RBD27. The effector packs against the switch and interswitch elements of Rab27a, and specific affinity toward Rab27a is modulated by a shift in the orientation of the effector structural motif (S/T)(G/L)xW(F/Y)(2). The observed structural complementation between the interacting surfaces of Rab27a and Exophilin4 sheds light on the disparities among the Rab27 effectors and outlines a general mechanism for their recruitment.

Reviews - 3bc1 mentioned but not cited (2)

  1. Structural mechanisms for regulation of membrane traffic by rab GTPases. Lee MT, Mishra A, Lambright DG. Traffic 10 1377-1389 (2009)
  2. Multivalency in Rab effector interactions. Rai A, Goody RS, Müller MP. Small GTPases 10 40-46 (2019)

Articles - 3bc1 mentioned but not cited (9)



Reviews citing this publication (9)

  1. Rab27 effectors, pleiotropic regulators in secretory pathways. Fukuda M. Traffic 14 949-963 (2013)
  2. Rab GTPases and their interacting protein partners: Structural insights into Rab functional diversity. Pylypenko O, Hammich H, Yu IM, Houdusse A. Small GTPases 9 22-48 (2018)
  3. Structures of Ras superfamily effector complexes: What have we learnt in two decades? Mott HR, Owen D. Crit Rev Biochem Mol Biol 50 85-133 (2015)
  4. Regulatory mechanisms of RANKL presentation to osteoclast precursors. Honma M, Ikebuchi Y, Kariya Y, Suzuki H. Curr Osteoporos Rep 12 115-120 (2014)
  5. Structural biology of Arf and Rab GTPases' effector recruitment and specificity. Khan AR, Ménétrey J. Structure 21 1284-1297 (2013)
  6. Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors. Catz SD. J Leukoc Biol 94 613-622 (2013)
  7. Therapeutic targeting of neutrophil exocytosis. Catz SD, McLeish KR. J Leukoc Biol 107 393-408 (2020)
  8. In vivo Roles of Rab27 and Its Effectors in Exocytosis. Izumi T. Cell Struct Funct 46 79-94 (2021)
  9. Extracellular Vesicles (EVs) in Tumor Diagnosis and Therapy. Tan M, Ge Y, Wang X, Wang Y, Liu Y, He F, Teng H. Technol Cancer Res Treat 22 15330338231171463 (2023)

Articles citing this publication (25)



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