3ay5 | pdb_00003ay5

Crystal structure of HHM (human homologue of murine maternal Id-like molecule)

spinqualitylabelsall models 3ay5, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ay5 is a 1 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 2.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CCDB1_HUMAN May negatively regulate cell cycle progression. May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking E2F-dependent transcription. Publication Abstract from PubMed Helix-loop-helix (HLH) family transcription factors regulate numerous developmental and homeostatic processes. Dominant-negative HLH (dnHLH) proteins lack DNA-binding ability and capture basic HLH (bHLH) transcription factors to inhibit cellular differentiation and enhance cell proliferation and motility, thus participating in patho-physiological processes. We report the first structure of a free-standing human dnHLH protein, HHM (Human homologue of murine maternal Id-like molecule). HHM adopts a V-shaped conformation, with N-terminal and C-terminal five-helix bundles connected by the HLH region. In striking contrast to the common HLH, the HLH region in HHM is extended, with its hydrophobic dimerization interfaces embedded in the N- and C-terminal helix bundles. Biochemical and physicochemical analyses revealed that HHM exists in slow equilibrium between this V-shaped form and the partially unfolded, relaxed form. The latter form is readily available for interactions with its target bHLH transcription factors. Mutations disrupting the interactions in the V-shaped form compromised the target transcription factor specificity and accelerated myogenic cell differentiation. Therefore, the V-shaped form of HHM may represent an autoinhibited state, and the dynamic conformational equilibrium may control the target specificity. Structure of a dominant-negative helix-loop-helix transcriptional regulator suggests mechanisms of autoinhibition.,Ishii R, Isogaya K, Seto A, Koinuma D, Watanabe Y, Arisaka F, Yaguchi S, Ikushima H, Dohmae N, Miyazono K, Miyazawa K, Ishitani R, Nureki O EMBO J. 2012 Mar 27;31(11):2541-52. doi: 10.1038/emboj.2012.77. PMID:22453338 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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