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6c48

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Crystal structure of B-Myb-LIN9-LIN52 complex

Structural highlights

6c48 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.32Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LIN9_HUMAN Acts as a tumor suppressor. Inhibits DNA synthesis. Its ability to inhibit oncogenic transformation is mediated through its association with RB1. Plays a role in the expression of genes required for the G1/S transition.^[1] ^[2]

Publication Abstract from PubMed

The MuvB transcriptional regulatory complex, which controls cell-cycle-dependent gene expression, cooperates with B-Myb to activate genes required for the G2 and M phases of the cell cycle. We have identified the domain in B-Myb that is essential for the assembly of the Myb-MuvB (MMB) complex. We determined a crystal structure that reveals how this B-Myb domain binds MuvB through the adaptor protein LIN52 and the scaffold protein LIN9. The structure and biochemical analysis provide an understanding of how oncogenic B-Myb is recruited to regulate genes required for cell-cycle progression, and the MMB interface presents a potential therapeutic target to inhibit cancer cell proliferation.

Structural mechanism of Myb-MuvB assembly.,Guiley KZ, Iness AN, Saini S, Tripathi S, Lipsick JS, Litovchick L, Rubin SM Proc Natl Acad Sci U S A. 2018 Sep 17. pii: 1808136115. doi:, 10.1073/pnas.1808136115. PMID:30224471^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gagrica S, Hauser S, Kolfschoten I, Osterloh L, Agami R, Gaubatz S. Inhibition of oncogenic transformation by mammalian Lin-9, a pRB-associated protein. EMBO J. 2004 Nov 24;23(23):4627-38. Epub 2004 Nov 11. PMID:15538385 doi:http://dx.doi.org/7600470
↑ Sandoval R, Xue J, Tian X, Barrett K, Pilkinton M, Ucker DS, Raychaudhuri P, Kineman RD, Luque RM, Baida G, Zou X, Valli VE, Cook JL, Kiyokawa H, Colamonici OR. A mutant allele of BARA/LIN-9 rescues the cdk4-/- phenotype by releasing the repression on E2F-regulated genes. Exp Cell Res. 2006 Aug 1;312(13):2465-75. Epub 2006 Apr 25. PMID:16730350 doi:http://dx.doi.org/S0014-4827(06)00156-X
↑ Guiley KZ, Iness AN, Saini S, Tripathi S, Lipsick JS, Litovchick L, Rubin SM. Structural mechanism of Myb-MuvB assembly. Proc Natl Acad Sci U S A. 2018 Sep 17. pii: 1808136115. doi:, 10.1073/pnas.1808136115. PMID:30224471 doi:http://dx.doi.org/10.1073/pnas.1808136115