6CKO

Crystal structure of an AF10 fragment

PDB DOI: https://doi.org/10.2210/pdb6CKO/pdb

Classification: DNA BINDING PROTEIN/TRANSFERASE
Organism(s): Homo sapiens, Danio rerio
Expression System: Escherichia coli BL21(DE3), Escherichia coli
Mutation(s): No

Deposited: 2018-02-28 Released: 2018-03-21
Deposition Author(s): Zhang, H., Tempel, W., Bountra, C., Arrowsmith, C.H., Edwards, A.M., Min, J., Structural Genomics Consortium (SGC)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.233
R-Value Work: 0.208
R-Value Observed: 0.209

wwPDB Validation 3D Report Full Report

This is version 1.1 of the entry. See complete history.

Literature

Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis.

Zhang, H., Zhou, B., Qin, S., Xu, J., Harding, R., Tempel, W., Nayak, V., Li, Y., Loppnau, P., Dou, Y., Min, J.

(2018) Genes Dev 32: 341-346

PubMed: 29563185 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1101/gad.311639.118
Primary Citation of Related Structures:
6CKN, 6CKO

PubMed Abstract:
The mixed-lineage leukemia (MLL)-AF10 fusion oncoprotein recruits DOT1L to the homeobox A ( HOXA ) gene cluster through its octapeptide motif leucine zipper (OM-LZ), thereby inducing and maintaining the MLL-AF10-associated leukemogenesis. However, the recognition mechanism between DOT1L and MLL-AF10 is unclear. Here, we present the crystal structures of both apo AF10 ^OM-LZ and its complex with the coiled-coil domain of DOT1L. Disruption of the DOT1L-AF10 interface abrogates MLL-AF10-associated leukemic transformation. We further show that zinc stabilizes the DOT1L-AF10 complex and may be involved in the regulation of the HOXA gene expression. Our studies may also pave the way for the rational design of therapeutic drugs against MLL -rearranged leukemia.

Organizational Affiliation

Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.

Macromolecule Content

Total Structure Weight: 29.85 kDa
Atom Count: 1,858
Modelled Residue Count: 233
Deposited Residue Count: 254
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Protein AF-10	A, B	77	Homo sapiens	Mutation(s): 0 Gene Names: MLLT10, AF10
UniProt & NIH Common Fund Data Resources
Find proteins for P55197 (Homo sapiens) Explore P55197 Go to UniProtKB: P55197
PHAROS: P55197 GTEx: ENSG00000078403
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P55197
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Histone-lysine N-methyltransferase, H3 lysine-79 specific	C, D	50	Danio rerio	Mutation(s): 0 Gene Names: dot1l EC: 2.1.1.43
UniProt
Find proteins for F1Q4W7 (Danio rerio) Explore F1Q4W7 Go to UniProtKB: F1Q4W7
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	F1Q4W7
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 E [auth A] SDF format, chain EA [auth D] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain P [auth B] SDF format, chain Q [auth B] SDF format, chain R [auth B] SDF format, chain W [auth C] MOL2 format, chain E [auth A] MOL2 format, chain EA [auth D] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain P [auth B] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth B] MOL2 format, chain W [auth C]	E [auth A] EA [auth D] F [auth A] G [auth A] P [auth B] E [auth A], EA [auth D], F [auth A], G [auth A], P [auth B], Q [auth B], R [auth B], W [auth C]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain EA [auth D] Focus chain F [auth A] Focus chain G [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Focus chain W [auth C] Interactions & Density Focus chain E [auth A] Focus chain EA [auth D] Focus chain F [auth A] Focus chain G [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Focus chain W [auth C]
UNX Query on UNX Download Ideal Coordinates CCD File SDF format, chain AA [auth C] SDF format, chain BA [auth C] SDF format, chain CA [auth C] SDF format, chain DA [auth C] SDF format, chain FA [auth D] SDF format, chain GA [auth D] SDF format, chain H [auth A] SDF format, chain HA [auth D] SDF format, chain I [auth A] SDF format, chain IA [auth D] SDF format, chain J [auth A] SDF format, chain JA [auth D] SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain M [auth A] SDF format, chain N [auth A] SDF format, chain O [auth A] SDF format, chain S [auth B] SDF format, chain T [auth B] SDF format, chain U [auth B] SDF format, chain V [auth B] SDF format, chain X [auth C] SDF format, chain Y [auth C] SDF format, chain Z [auth C] MOL2 format, chain AA [auth C] MOL2 format, chain BA [auth C] MOL2 format, chain CA [auth C] MOL2 format, chain DA [auth C] MOL2 format, chain FA [auth D] MOL2 format, chain GA [auth D] MOL2 format, chain H [auth A] MOL2 format, chain HA [auth D] MOL2 format, chain I [auth A] MOL2 format, chain IA [auth D] MOL2 format, chain J [auth A] MOL2 format, chain JA [auth D] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] MOL2 format, chain N [auth A] MOL2 format, chain O [auth A] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] MOL2 format, chain V [auth B] MOL2 format, chain X [auth C] MOL2 format, chain Y [auth C] MOL2 format, chain Z [auth C]	AA [auth C] BA [auth C] CA [auth C] DA [auth C] FA [auth D] AA [auth C], BA [auth C], CA [auth C], DA [auth C], FA [auth D], GA [auth D], H [auth A], HA [auth D], I [auth A], IA [auth D], J [auth A], JA [auth D], K [auth A], L [auth A], M [auth A], N [auth A], O [auth A], S [auth B], T [auth B], U [auth B], V [auth B], X [auth C], Y [auth C], Z [auth C]	UNKNOWN ATOM OR ION X		Interactions Focus chain AA [auth C] Focus chain BA [auth C] Focus chain CA [auth C] Focus chain DA [auth C] Focus chain FA [auth D] Focus chain GA [auth D] Focus chain H [auth A] Focus chain HA [auth D] Focus chain I [auth A] Focus chain IA [auth D] Focus chain J [auth A] Focus chain JA [auth D] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain X [auth C] Focus chain Y [auth C] Focus chain Z [auth C] Interactions & Density Focus chain AA [auth C] Focus chain BA [auth C] Focus chain CA [auth C] Focus chain DA [auth C] Focus chain FA [auth D] Focus chain GA [auth D] Focus chain H [auth A] Focus chain HA [auth D] Focus chain I [auth A] Focus chain IA [auth D] Focus chain J [auth A] Focus chain JA [auth D] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain X [auth C] Focus chain Y [auth C] Focus chain Z [auth C]