1MV0

NMR STRUCTURE OF THE TUMOR SUPPRESSOR BIN1: ALTERNATIVE SPLICING IN MELANOMA AND INTERACTION WITH C-MYC

Summary for 1MV0

• Entry DOI: 10.2210/pdb1mv0/pdb
• Related: 1MUZ 1MV3
• Descriptor: Myc proto-oncogene protein, Myc box-dependent-interacting protein 1 (2 entities in total)
• Functional Keywords: tumor suppressor/oncoprotein, endocytosis/exocytosis, transcription complex, endocytosis-exocytosis, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus, nucleoplasm: P01106; Isoform BIN1: Nucleus. Isoform IIA: Cytoplasm: O00499
• Total number of polymer chains: 2
• Total formula weight: 10836.20

Authors

Pineda-Lucena, A.,Arrowsmith, C.H. (deposition date: 2002-09-24, release date: 2003-09-30, Last modification date: 2024-05-22)

Primary citation

Pineda-Lucena, A.,Ho, C.S.,Mao, D.Y.,Sheng, Y.,Laister, R.C.,Muhandiram, R.,Lu, Y.,Seet, B.T.,Katz, S.,Szyperski, T.,Penn, L.Z.,Arrowsmith, C.H.
A structure-based model of the c-Myc/Bin1 protein interaction shows alternative splicing of Bin1 and c-Myc phosphorylation are key binding determinants.
J.Mol.Biol., 351:182-194, 2005

PubMed Abstract: The N terminus of the c-Myc oncoprotein interacts with Bin1, a ubiquitously expressed nucleocytoplasmic protein with features of a tumor suppressor. The c-Myc/Bin1 interaction is dependent on the highly conserved Myc Box 1 (MB1) sequence of c-Myc. The c-Myc/Bin1 interaction has potential regulatory significance as c-Myc-mediated transformation and apoptosis can be modulated by the expression of Bin1. Multiple splicing of the Bin1 transcript results in ubiquitous, tissue-specific and tumor-specific populations of Bin1 proteins in vivo. We report on the structural features of the interaction between c-Myc and Bin1, and describe two mechanisms by which the binding of different Bin1 isoforms to c-Myc may be regulated in cells. Our findings identify a consensus class II SH3-binding motif in c-Myc and the C-terminal SH3 domain of Bin1 as the primary structure determinants of their interaction. We present biochemical and structural evidence that tumor-specific isoforms of Bin1 are precluded from interaction with c-Myc through an intramolecular polyproline-SH3 domain interaction that inhibits the Bin1 SH3 domain from binding to c-Myc. Furthermore, c-Myc/Bin1 interaction can be inhibited by phosphorylation of c-Myc at Ser62, a functionally important residue found within the c-Myc SH3-binding motif. Our data provide a structure-based model of the c-Myc/Bin1 interaction and suggest a mode of regulation that may be important for c-Myc function as a regulator of gene transcription.

PubMed: 15992821
DOI: 10.1016/j.jmb.2005.05.046

Experimental method

SOLUTION NMR