2L0T

Solution structure of the complex of ubiquitin and the VHS domain of Stam2

Summary for 2L0T

• Entry DOI: 10.2210/pdb2l0t/pdb
• Related: 1D3Z 1X5B
• Descriptor: Ubiquitin, Signal transducing adapter molecule 2 (2 entities in total)
• Functional Keywords: ubiquitin, vhs, stam2, endosome, transport, protein transport
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm (By similarity): O75886
• Total number of polymer chains: 2
• Total formula weight: 26262.05

Authors

Lange, A.,Hoeller, D.,Wienk, H.,Marcillat, O.,Lancelin, J.,Walker, O. (deposition date: 2010-07-15, release date: 2010-12-15, Last modification date: 2024-05-01)

Primary citation

Lange, A.,Hoeller, D.,Wienk, H.,Marcillat, O.,Lancelin, J.M.,Walker, O.
NMR reveals a different mode of binding of the Stam2 VHS domain to ubiquitin and diubiquitin.
Biochemistry, 50:48-62, 2011

PubMed 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.

PubMed: 21121635
DOI: 10.1021/bi101594a

Experimental method

SOLUTION NMR