9C5S
Disulfide-linked, antiparallel p53-derived peptide dimer (CV1)
Summary for 9C5S
| Entry DOI | 10.2210/pdb9c5s/pdb |
| Descriptor | Cellular tumor antigen p53, SULFATE ION (3 entities in total) |
| Functional Keywords | antiparallel dimer, p53, unknown function |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 6808.03 |
| Authors | Vithanage, N.,Kreitler, D.K.,DiGiorno, M.C.,Victorio, C.G.,Sawyer, N.,Outlaw, V.K. (deposition date: 2024-06-06, release date: 2024-06-26, Last modification date: 2024-10-16) |
| Primary citation | DiGiorno, M.C.,Vithanage, N.,Victorio, C.G.,Kreitler, D.F.,Outlaw, V.K.,Sawyer, N. Structural Characterization of Disulfide-Linked p53-Derived Peptide Dimers. Res Sq, 2024 Cited by PubMed Abstract: Disulfide bonds provide a convenient method for chemoselective alteration of peptide and protein structure and function. We previously reported that mild oxidation of a p53-derived bisthiol peptide (CTFANLWRLLAQNC) under dilute non-denaturing conditions led to unexpected disulfide-linked dimers as the exclusive product. The dimers were antiparallel, significantly α-helical, resistant to protease degradation, and easily reduced back to the original bisthiol peptide. Here we examine the intrinsic factors influencing peptide dimerization using a combination of amino acid substitution, circular dichroism (CD) spectroscopy, and X-ray crystallography. CD analysis of peptide variants suggests critical roles for Leu6 and Leu10 in the formation of stable disulfide-linked dimers. The 1.0 Å resolution crystal structure of the peptide dimer supports these data, revealing a leucine-rich LxxLL dimer interface with canonical knobs-into-holes packing. Two levels of higher-order oligomerization are also observed in the crystal: an antiparallel "dimer of dimers" mediated by Phe3 and Trp7 residues in the asymmetric unit and a tetramer of dimers mediated by Trp7 and Leu10. In CD spectra of Trp-containing peptide variants, minima at 227 nm provide evidence for the dimer of dimers in dilute aqueous solution. Importantly, and in contrast to the original dimer model, the canonical leucine-rich core and robust dimerization of most peptide variants suggests a tunable molecular architecture to target various proteins and evaluate how folding and oligomerization impact various properties, such as cell permeability. PubMed: 39070635DOI: 10.21203/rs.3.rs-4644285/v1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.01 Å) |
Structure validation
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