2NL9

Crystal structure of the Mcl-1:Bim BH3 complex

PDB DOI: https://doi.org/10.2210/pdb2NL9/pdb

Classification: APOPTOSIS
Organism(s): Mus musculus, Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2006-10-19 Released: 2007-03-27
Deposition Author(s): Czabotar, P.E., Colman, P.M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.55 Å
R-Value Free: 0.203
R-Value Work: 0.173
R-Value Observed: 0.174

wwPDB Validation 3D Report Full Report

This is version 1.5 of the entry. See complete history.

Literature

Structural insights into the degradation of Mcl-1 induced by BH3 domains.

Czabotar, P.E., Lee, E.F., van Delft, M.F., Day, C.L., Smith, B.J., Huang, D.C., Fairlie, W.D., Hinds, M.G., Colman, P.M.

(2007) Proc Natl Acad Sci U S A 104: 6217-6222

PubMed: 17389404 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1073/pnas.0701297104
Primary Citation of Related Structures:
2JM6, 2NL9, 2NLA

PubMed Abstract:
Apoptosis is held in check by prosurvival proteins of the Bcl-2 family. The distantly related BH3-only proteins bind to and antagonize them, thereby promoting apoptosis. Whereas binding of the BH3-only protein Noxa to prosurvival Mcl-1 induces Mcl-1 degradation by the proteasome, binding of another BH3-only ligand, Bim, elevates Mcl-1 protein levels. We compared the three-dimensional structures of the complexes formed between BH3 peptides of both Bim and Noxa, and we show that a discrete C-terminal sequence of the Noxa BH3 is necessary to instigate Mcl-1 degradation.

Organizational Affiliation

The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.

Macromolecule Content

Total Structure Weight: 21.68 kDa
Atom Count: 1,602
Modelled Residue Count: 165
Deposited Residue Count: 183
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
FUSION PROTEIN CONSISTING OF Induced myeloid leukemia cell differentiation protein Mcl-1 homolog	A	157	Mus musculus, Homo sapiens This entity is chimeric	Mutation(s): 0 Gene Names: Mcl1
UniProt & NIH Common Fund Data Resources
Find proteins for P97287 (Mus musculus) Explore P97287 Go to UniProtKB: P97287
IMPC: MGI:101769
Find proteins for Q07820 (Homo sapiens) Explore Q07820 Go to UniProtKB: Q07820
PHAROS: Q07820 GTEx: ENSG00000143384
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Groups	P97287Q07820
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Bcl-2-like protein 11	B	26	Homo sapiens	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for O43521 (Homo sapiens) Explore O43521 Go to UniProtKB: O43521
PHAROS: O43521 GTEx: ENSG00000153094
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O43521
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain J [auth B] SDF format, chain F [auth A] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain J [auth B] MOL2 format, chain F [auth A] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain J [auth B] mmCIF format, chain F [auth A]	C [auth A] D [auth A] E [auth A] F [auth A] G [auth A] C [auth A], D [auth A], E [auth A], F [auth A], G [auth A], H [auth A], J [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain J [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain J [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain I [auth A] MOL2 format, chain I [auth A] mmCIF format, chain I [auth A]	I [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain I [auth A] Interactions & Density Focus chain I [auth A]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
MSE Query on MSE	A	L-PEPTIDE LINKING	C₅ H₁₁ N O₂ Se		MET

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.55 Å
R-Value Free: 0.203
R-Value Work: 0.173
R-Value Observed: 0.174
Space Group: I 2 2 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 52.38	α = 90
b = 70.08	β = 90
c = 117.18	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
PDB_EXTRACT	data extraction
HKL-2000	data collection
HKL-2000	data reduction
HKL-2000	data scaling
SHELXE	model building

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2007-03-27

Deposition Author(s):

Czabotar, P.E.

Colman, P.M.

Revision History (Full details and data files)

Version 1.0: 2007-03-27
Type: Initial release
Version 1.1: 2008-05-01
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Derived calculations, Version format compliance
Version 1.3: 2017-06-14
Changes: Source and taxonomy
Version 1.4: 2023-12-27
Changes: Advisory, Data collection, Database references, Derived calculations
Version 1.5: 2024-10-30
Changes: Structure summary