2aze

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models PDB ID 2aze Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.55Å
Gene:	TFDP1, DP1 (Homo sapiens), E2F1, RBBP3 (Homo sapiens), RB1 (Homo sapiens)
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Structure of the Rb C-terminal domain bound to an E2F1-DP1 heterodimer

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The retinoblastoma (Rb) protein negatively regulates the G1-S transition by binding to the E2F transcription factors, until cyclin-dependent kinases phosphorylate Rb, causing E2F release. The Rb pocket domain is necessary for E2F binding, but the Rb C-terminal domain (RbC) is also required for growth suppression. Here we demonstrate a high-affinity interaction between RbC and E2F-DP heterodimers shared by all Rb and E2F family members. The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC. We also demonstrate that phosphorylation of RbC at serines 788 and 795 destabilizes one set of RbC-E2F-DP interactions directly, while phosphorylation at threonines 821 and 826 induces an intramolecular interaction between RbC and the Rb pocket that destabilizes the remaining interactions indirectly. Our findings explain the requirement of RbC for high-affinity E2F binding and growth suppression and establish a mechanism for the regulation of Rb-E2F association by phosphorylation.

Disease

Known disease associated with this structure: Bladder cancer OMIM:[180200], Osteosarcoma OMIM:[180200], Pinealoma with bilateral retinoblastoma OMIM:[180200], Retinoblastoma OMIM:[180200]

About this Structure

2AZE is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release., Rubin SM, Gall AL, Zheng N, Pavletich NP, Cell. 2005 Dec 16;123(6):1093-106. PMID:16360038

Page seeded by OCA on Mon Mar 31 01:59:23 2008