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NMR reveals a different mode of binding of the Stam2 VHS domain to ubiquitin and diubiquitin.

Lange A, Hoeller D, Wienk H, Marcillat O, Lancelin JM, Walker O
Biochemistry 50 48-62 (2011)
Cited: 5 times
EuropePMC logo PMID: 21121635

Abstract

The VHS domain of the Stam2 protein is a ubiquitin binding domain involved in the recognition of ubiquitinated proteins committed to lysosomal degradation. Among all VHS domains, the VHS domain of Stam proteins is the strongest binder to monoubiqiuitin and exhibits preferences for K63-linked chains. In the present paper, we report the solution NMR structure of the Stam2-VHS domain in complex with monoubiquitin by means of chemical shift perturbations, spin relaxation, and paramagnetic relaxation enhancements. We also characterize the interaction of Stam2-VHS with K48- and K63-linked diubiquitin chains and report the first evidence that VHS binds differently to these two chains. Our data reveal that VHS enters the hydrophobic pocket of K48-linked diubiquitin and binds the two ubiquitin subunits with different affinities. In contrast, VHS interacts with K63-linked diubiquitin in a mode similar to its interaction with monoubiquitin. We also suggest possible structural models for both K48- and K63-linked diubiquitin in interaction with VHS. Our results, which demonstrate a different mode of binding of VHS for K48- and K63-linked diubiquitin, may explain the preference of VHS for K63- over K48-linked diubiquitin chains and monoubiquitin.

Reviews citing this publication (2)

  1. Versatile roles of k63-linked ubiquitin chains in trafficking. Erpapazoglou Z, Walker O, Haguenauer-Tsapis R. Cells 3 1027-1088 (2014)
  2. Characterizing weak protein-protein complexes by NMR residual dipolar couplings. Jensen MR, Ortega-Roldan JL, Salmon L, van Nuland N, Blackledge M. Eur. Biophys. J. 40 1371-1381 (2011)

Articles citing this publication (3)

  1. A dual role for K63-linked ubiquitin chains in multivesicular body biogenesis and cargo sorting. Erpapazoglou Z, Dhaoui M, Pantazopoulou M, Giordano F, Giordano F, Mari M, Léon S, Raposo G, Reggiori F, Haguenauer-Tsapis R. Mol. Biol. Cell 23 2170-2183 (2012)
  2. Evidence for cooperative and domain-specific binding of the signal transducing adaptor molecule 2 (STAM2) to Lys63-linked diubiquitin. Lange A, Castañeda C, Hoeller D, Lancelin JM, Fushman D, Walker O. J. Biol. Chem. 287 18687-18699 (2012)
  3. Competitive binding of UBPY and ubiquitin to the STAM2 SH3 domain revealed by NMR. Lange A, Ismail MB, Rivière G, Hologne M, Lacabanne D, Guillière F, Lancelin JM, Krimm I, Walker O. FEBS Lett. 586 3379-3384 (2012)


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