5B1C

Crystal structure of DEN4 ED3 mutant with L387I

Summary for 5B1C

• Entry DOI: 10.2210/pdb5b1c/pdb
• Related: 3WE1 4X42
• Descriptor: Envelope protein E, SULFATE ION (3 entities in total)
• Functional Keywords: hydrophobic core residue, side-chain rotamers, point mutation, immune system
• Biological source: Dengue virus 4 Dominica/814669/1981 (DENV-4)
• Total number of polymer chains: 3
• Total formula weight: 34911.56

Authors

Kulkarni, M.R.,Numoto, N.,Ito, N.,Kuroda, Y. (deposition date: 2015-12-02, release date: 2016-02-24, Last modification date: 2024-10-23)

Primary citation

Kulkarni, M.R.,Numoto, N.,Ito, N.,Kuroda, Y.
Modeling and experimental assessment of a buried Leu-Ile mutation in dengue envelope domain III
Biochem.Biophys.Res.Commun., 471:163-168, 2016

PubMed Abstract: Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4_L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile(387) conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype's ED3 is used as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile(387) confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4_L387I at 2 Å resolution. Ile(387) indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task.

PubMed: 26826384
DOI: 10.1016/j.bbrc.2016.01.159

Experimental method

X-RAY DIFFRACTION (2.003 Å)