Evidence for cooperative and domain-specific binding of the signal transducing adaptor molecule 2 (STAM2) to lys(63)-linked diubiquitin

Abstract : As the upstream component of the ESCRT (endosomal sorting complexes required for transport) machinery, the ESCRT-0 complex is responsible for directing ubiquitinated membrane proteins to the multivesicular body pathway. ESCRT-0 is formed by two subunits known as Hrs (hepatocyte growth factor-regulated substrate) and STAM (signal transducing adaptor molecule), both of which harbor multiple ubiquitin-binding domains (UBDs). In particular, STAM2 possesses two UBDs, the VHS (Vps27/Hrs/Stam) and UIM (ubiquitin interacting motif) domains, connected by a 20-amino acid flexible linker. In the present study, we report the interactions of the UIM domain and VHS-UIM construct of STAM2 with monoubiquitin (Ub), Lys(48)- and Lys(63)-linked diubiquitins. Our results demonstrate that the UIM domain alone binds monoubiquitin, Lys(48)- and Lys(63)-linked diubiquitins with the same affinity and in the same binding mode. Interestingly, binding of VHS-UIM to Lys(63)-linked diubiquitin is not only avid, but also cooperative. We also show that the distal domain of Lys(63)-linked diubiquitin stabilizes the helical structure of the UIM domain and that the corresponding complex adopts a specific structural organization responsible for its greater affinity. In contrast, binding of VHS-UIM to Lys(48)-linked diubiquitin and monoubiquitin is not cooperative and does not show any avidity. These results may explain the better sorting efficiency of some cargoes polyubiquitinated with Lys(63)-linked chains over monoubiquitinated cargoes or those tagged with Lys(48)-linked chains.
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Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2012, 287 (22), pp.18687-18699. 〈10.1074/jbc.M111.324954〉
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Contributeur : Agnès Bussy <>
Soumis le : mercredi 16 octobre 2013 - 15:48:51
Dernière modification le : jeudi 8 février 2018 - 11:10:22

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Anja Lange, Carlos Castaneda, Daniela Hoeller, Jean-Marc Lancelin, David Fushman, et al.. Evidence for cooperative and domain-specific binding of the signal transducing adaptor molecule 2 (STAM2) to lys(63)-linked diubiquitin. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2012, 287 (22), pp.18687-18699. 〈10.1074/jbc.M111.324954〉. 〈hal-00873866〉

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