The structure of the c-Cbl-UbcH7 complex reveals how the RING domain of c-Cbl recruits the E2 ubiquitin-conjugating enzyme (UbcH7). The RING domain forms a rigid interface with the E2, and a conserved surface channel connects the substrate-binding site to the E2 active site, suggesting that RING E3s function as scaffolds to position the substrate and E2 optimally for ubiquitin transfer. The structure also shows that the RING domain and linker sequence interact extensively with the TKB domain, which is essential for c-Cbl function. The RING domain contains a shallow groove that binds the tips of UbcH7 loops, and the structure indicates that specific residues in UbcH7, such as Phe-63, are critical for E2 specificity. The structure of the c-Cbl-UbcH7 complex is similar to that of the E6AP-UbcH7 complex, suggesting that the UbcH7 E2 binds to both RING and HECT E3s in a similar manner. The rigid arrangement of the subunits in the complex and the conserved surface channel suggest that c-Cbl not only recruits the substrate and E2 but also contributes to the selection of lysine residues for ubiquitination. The structure provides insights into the mechanism of ubiquitination by RING E3s and highlights the importance of the RING domain in E3 function.The structure of the c-Cbl-UbcH7 complex reveals how the RING domain of c-Cbl recruits the E2 ubiquitin-conjugating enzyme (UbcH7). The RING domain forms a rigid interface with the E2, and a conserved surface channel connects the substrate-binding site to the E2 active site, suggesting that RING E3s function as scaffolds to position the substrate and E2 optimally for ubiquitin transfer. The structure also shows that the RING domain and linker sequence interact extensively with the TKB domain, which is essential for c-Cbl function. The RING domain contains a shallow groove that binds the tips of UbcH7 loops, and the structure indicates that specific residues in UbcH7, such as Phe-63, are critical for E2 specificity. The structure of the c-Cbl-UbcH7 complex is similar to that of the E6AP-UbcH7 complex, suggesting that the UbcH7 E2 binds to both RING and HECT E3s in a similar manner. The rigid arrangement of the subunits in the complex and the conserved surface channel suggest that c-Cbl not only recruits the substrate and E2 but also contributes to the selection of lysine residues for ubiquitination. The structure provides insights into the mechanism of ubiquitination by RING E3s and highlights the importance of the RING domain in E3 function.