title: Just a Flexible Linker? The Structural and Dynamic Properties of CBP-ID4 Revealed by NMR Spectroscopy.
abstract: Here, we present a structural and dynamic description of CBP-ID4 at atomic resolution. ID4 is the fourth intrinsically disordered linker of CREB-binding protein (CBP). In spite of the largely disordered nature of CBP-ID4, NMR chemical shifts and relaxation measurements show a significant degree of α-helix sampling in the protein regions encompassing residues 2-25 and 101-128 (1852-1875 and 1951-1978 in full-length CBP). Proline residues are uniformly distributed along the polypeptide, except for the two α-helical regions, indicating that they play an active role in modulating the structural features of this CBP fragment. The two helical regions are lacking known functional motifs, suggesting that they represent thus-far uncharacterized functional modules of CBP. This work provides insights into the functions of this protein linker that may exploit its plasticity to modulate the relative orientations of neighboring folded domains of CBP and fine-tune its interactions with a multitude of partners.
authors.affiliation: Magnetic Resonance Center, University of Florence, Florence, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piai
authors.affiliation: Magnetic Resonance Center, University of Florence, Florence, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Florence, Italy.
authors.forename: Eduardo O
authors.initials: EO
authors.lastname: Calçada
authors.affiliation: Magnetic Resonance Center, University of Florence, Florence, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Florence, Italy.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tarenzi
authors.affiliation: Magnetic Resonance Center, University of Florence, Florence, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Florence, Italy.
authors.forename: Alessandro Del
authors.initials: AD
authors.lastname: Grande
authors.affiliation: VIB Structural Biology Research Center, Vlaams Instituut voor Biotechnologie at Vrije Universiteit Brussel, Brussel, Belgium.
authors.forename: Mihaly
authors.initials: M
authors.lastname: Varadi
authors.affiliation: VIB Structural Biology Research Center, Vlaams Instituut voor Biotechnologie at Vrije Universiteit Brussel, Brussel, Belgium; Institute of Enzymology, Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Tompa
authors.affiliation: Magnetic Resonance Center, University of Florence, Florence, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Florence, Italy. Electronic address: felli@cerm.unifi.it.
authors.forename: Isabella C
authors.initials: IC
authors.lastname: Felli
authors.affiliation: Magnetic Resonance Center, University of Florence, Florence, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Florence, Italy. Electronic address: pierattelli@cerm.unifi.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pierattelli
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D050882:CREB-Binding Protein / Q000737:chemistry*; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary
chemical_list: C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins; D050882:CREB-Binding Protein