9ERZ: CBL-TKBD

Structure of CBL-TKBD bound to Ubiquitin-fused CBLock peptide. Determined by X-ray diffraction at 2.02 Å resolution. Released 14 May 2025.

Method: X-ray diffraction
Resolution: 2.02 Å
Organism: Homo sapiens
Chains: 4
Atoms: 6,415
Mol. weight: 96.27 kDa
Ligands: CA
Released: 14 May 2025

Explore 9ERZ in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9ERZ contains 48 α-helices and 29 β-strands across 4 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 20 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	49-51	3
α-helix	53-70	18
α-helix	73-75	3
α-helix	84-102	19
α-helix	106-111	6
α-helix	113-136	24
α-helix	137-141	5
α-helix	146-168	23
α-helix	176-178	3
α-helix	184-194	11
β-strand	199-201	3	1
α-helix	202-212	11
α-helix	218-228	11
β-strand	235-237	3	1
α-helix	238-247	10
α-helix	251-253	3
α-helix	254-258	5
α-helix	259-263	5
β-strand	268-271	4	2
α-helix	274-281	8
α-helix	282-284	3
β-strand	290-295	6	2
β-strand	303-308	6	2
β-strand	314-317	4	2
α-helix	324-334	11
β-strand	339-340	2	2
α-helix	350-352	3

Chain B: 5 helices, 7 β-strands

Element	Residues	Length	Sheet
β-strand	2-6	5	3
β-strand	12-16	5	3
β-strand	22	1	4
α-helix	23-34	12
α-helix	38-40	3
β-strand	43-45	3	3
β-strand	48-49	2	3
α-helix	50-51	2
β-strand	55	1	4
β-strand	66-69	4	3
α-helix	80-82	3
α-helix	83-92	10

Chain C: 18 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	53-70	18
α-helix	73-75	3
α-helix	84-101	18
α-helix	106-111	6
α-helix	113-136	24
α-helix	137-141	5
α-helix	146-168	23
α-helix	176-178	3
α-helix	184-194	11
β-strand	199-201	3	5
α-helix	202-210	9
α-helix	218-228	11
β-strand	235-237	3	5
α-helix	238-247	10
α-helix	251-253	3
α-helix	254-258	5
α-helix	259-263	5
β-strand	268-271	4	6
α-helix	274-282	9
β-strand	290-295	6	6
β-strand	303-308	6	6
β-strand	314-317	4	6
α-helix	324-333	10
β-strand	339-340	2	6
α-helix	350-352	3

Chain D: 5 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	2-5	4	7
β-strand	13-16	4	7
β-strand	22	1	8
α-helix	23-34	12
α-helix	38-40	3
β-strand	41-44	4	9
β-strand	49	1	9
β-strand	55	1	8
α-helix	57-59	3
β-strand	66-67	2	7
β-strand	68-71	4	9
α-helix	80-82	3
α-helix	83-92	10

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
E3 ubiquitin-protein ligase CBL	A, C	protein	311	Homo sapiens	P22681 (AlphaFold model)
Polyubiquitin-C,Ub-fused CBLock peptide	B, D	protein	107	Homo sapiens	P0CG48 (AlphaFold model)

Sequence of entity 1 (A, C), FASTA

>9ERZ_1 E3 ubiquitin-protein ligase CBL (chains A, C)
GSPPGTVDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTILSRYEG
KMETLGENEYFRVFMENLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAE
LKGIFPSGLFQGDTFRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMAL
KSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNWNSLAVTHPGYMAFLTYDEVKARLQKF
IHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGRN
QNPDLTGLCEP

Sequence of entity 2 (B, D), FASTA

>9ERZ_2 Polyubiquitin-C,Ub-fused CBLock peptide (chains B, D)
GSGGSMQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRT
LSDYNIQKESTLHLVLRLRAAPGGSMTVEEMDSWIKSWDQMHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
CA	Calcium ion	Ca	2

Primary citation

Locking CBL TKBD in its native conformation presents a novel therapeutic opportunity in mutant CBL-dependent leukemia. Ahmed, S.F., Anand, J., Zhang, W. et al. Mol Ther (2025) 33:3624-3643. DOI 10.1016/j.ymthe.2025.04.042 · PubMed

Other PDB entries of the same protein (UniProt P22681 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3BUX 1.35 Å, Crystal structure of c-Cbl-TKB domain complexed with its binding motif in c-Met
3BUW 1.45 Å, Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Syk
7SIY 1.48 Å, cCBL TKB domain in complex with pZAP70 peptide
5HKY 1.8 Å, Crystal structure of c-Cbl TKBD domain in complex with SPRY2 peptide (36-60, pY55)…
5HKZ 1.8 Å, Crystal Structure of c-Cbl TKBD in complex with SPRY2 peptide (36-60, pY55) Refined to…
5HKX 1.85 Å, Crystal Structure of c-Cbl TKBD-RING domains (Y371E mutant) Refined to 1.85 A Resolution
3PLF 1.92 Å, Reverse Binding Mode of MetRD peptide complexed with c-Cbl TKB domain
2Y1N 2.0 Å, Structure of c-Cbl-ZAP-70 peptide complex
3BUM 2.0 Å, Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty2
3BUN 2.0 Å, Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty4
1YVH 2.05 Å, Crystal Structure of the c-Cbl TKB Domain in Complex with the APS pTyr-618 Phosphopeptide
2CBL 2.1 Å, N-terminal domain of cbl in complex with its binding site on zap-70

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