Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis of NSD2 degradation via targeted recruitment of SCF-FBXO22.
Journal, issue, pages	Nat Commun, Year 2026
Publish date	Apr 23, 2026
Authors	Kevin C Robertson / Sascha J Amann / Tongkun Liu / Adam V Funk / Xianxi Wang / Irina Grishkovskaya / Aamir Mehmood / John R Tabor / Jacqueline L Norris-Drouin / Cheryl H Arrowsmith / Jon L Collins / Yinglong Miao / Michael J Emanuele / David Haselbach / Lindsey I James / Nicholas G Brown /
PubMed Abstract	Targeted protein degradation (TPD) through the ubiquitin-proteasome system is driven by compound-mediated polyubiquitination of a protein-of-interest by an E3 ubiquitin (Ub) ligase. Relatively few ...Targeted protein degradation (TPD) through the ubiquitin-proteasome system is driven by compound-mediated polyubiquitination of a protein-of-interest by an E3 ubiquitin (Ub) ligase. Relatively few E3s have been successfully utilized for TPD and the governing principles of functional ternary complex formation between the E3, degrader, and protein target remain elusive. FBXO22 has recently been harnessed for TPD applications by degraders that covalently modify its cysteine residues. Here, we reveal that the aldehyde derivative of UNC10088 promotes cooperative binding of FBXO22 to NSD2, a histone methyltransferase and oncogenic protein, leading to a cryo-EM structure of the SKP1-CUL1-F-box (SCF)-FBXO22 complex with NSD2. This structure revealed a conformational change in the FBXO22 loop surrounding C326, further exposing the cysteine for covalent recruitment. Additional medicinal chemistry efforts led to the discovery of benzaldehyde-based non-prodrug degraders that similarly engage C326 of FBXO22 and potently degrade NSD2. Unlike many degraders, our molecules recruit NSD2 to a different surface of FBXO22 than the known FBXO22 substrate BACH1, allowing for concurrent complex formation and structural determination of SCF bound to both the neosubstrate NSD2 and native substrate BACH1. Overall, we demonstrate the biochemical and structural basis for NSD2 degradation, revealing key principles for efficient and selective TPD by SCF.
External links	Nat Commun / PubMed:42026065
Methods	EM (single particle)
Resolution	3.34 - 7.04 Å
Structure data	57178 29hg EMDB-57178, PDB-29hg: Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10088 Method: EM (single particle) / Resolution: 4.0 Å 57179 29hh EMDB-57179, PDB-29hh: Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2, UNC10088 and Bach1 Method: EM (single particle) / Resolution: 4.2 Å 57180 29hi EMDB-57180, PDB-29hi: Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10415667 Method: EM (single particle) / Resolution: 5.9 Å EMDB-57298: SKP1-FBXO22-UNC10088-NSD2 locally refined Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10088 Method: EM (single particle) / Resolution: 4.07 Å EMDB-57299: CUL1 locally refined Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10088 Method: EM (single particle) / Resolution: 3.34 Å EMDB-57301: CUL1 C-term, RBX1 locally refined Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10088 Method: EM (single particle) / Resolution: 3.84 Å EMDB-57302: Consensus Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10088 Method: EM (single particle) / Resolution: 4.08 Å EMDB-57303: SKP1-FBXO22-UNC10088-NSD2 locally refined Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10088 and Bach1 Method: EM (single particle) / Resolution: 4.31 Å EMDB-57304: CUL1-C-terminus-RBX1 locally refined Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10088 and Bach1 Method: EM (single particle) / Resolution: 4.1 Å EMDB-57305: SKP1-CUL1 locally refined Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10088 and Bach1 Method: EM (single particle) / Resolution: 4.5 Å EMDB-57306: Consensus Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10088 and Bach1 Method: EM (single particle) / Resolution: 7.04 Å EMDB-57308: SKP1-FBXO22-UNC10088-NSD2 locally refined Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10415667 Method: EM (single particle) / Resolution: 5.87 Å EMDB-57309: CUL1 locally refined Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10415667 Method: EM (single particle) / Resolution: 4.59 Å EMDB-57310: CUL1 C-term, RBX1 locally refined Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10415667 Method: EM (single particle) / Resolution: 5.22 Å EMDB-57311: Consensus Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO22 SCF ubiquition ligase in complex with NSD2 via UNC10415667 Method: EM (single particle) / Resolution: 5.7 Å
Chemicals	PDB-1j20: Crystal Structure of Thermus thermophilus HB8 Argininosuccinate Synthetase in complex with product PDB-1j21: Crystal Structure of Thermus thermophilus HB8 Argininosuccinate Synthetase in complex with ATP and citrulline
Source	homo sapiens (human)
Keywords	LIGASE / Ubiquitin Ligase / Targeted protein degradation / cullin-RING ligase / SKP1 CUL1 F box SCF / Nuclear receptor binding SET domain-containing 2 NSD2