4LPY

Crystal structure of TENCON variant G10

4LPY の概要

• エントリーDOI: 10.2210/pdb4lpy/pdb
• 関連するPDBエントリー: 4LPT 4LPU 4LPV 4LPW 4LPX
• 分子名称: TENCON variant G10, SODIUM ION (3 entities in total)
• 機能のキーワード: fibronectin type iii fold, alternate scaffold, de novo protein
• 由来する生物種: artificial gene
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22317.89

構造登録者

Teplyakov, A.,Obmolova, G.,Gilliland, G.L. (登録日: 2013-07-16, 公開日: 2014-01-29, 最終更新日: 2023-09-20)

主引用文献

Teplyakov, A.,Obmolova, G.,Malia, T.J.,Luo, J.,Jacobs, S.A.,Chan, W.,Domingo, D.,Baker, A.,O'Neil, K.T.,Gilliland, G.L.
C-terminal beta-strand swapping in a consensus-derived fibronectin Type III scaffold.
Proteins, 82:1359-1369, 2014

PubMed Abstract: The crystal structures of six different fibronectin Type III consensus-derived Tencon domains, whose solution properties exhibit no, to various degrees of, aggregation according to SEC, have been determined. The structures of the five variants showing aggregation reveal 3D domain swapped dimers. In all five cases, the swapping involves the C-terminal β-strand resulting in the formation of Tencon dimers in which the target-binding surface is blocked. All of the variants differ in sequence in the FG loop, which is the hinge loop in the β-strand-swapped dimers. The six tencon variants have between 0 and 5 residues inserted between positions 77 and 78 in the FG loop. Analysis of the structures suggests that a non-glycine residue at position 77 and insertions of <4 residues may destabilize the β-turn in the FG loop promoting β-strand swapping. Swapped dimers with an odd number of inserted residues may be less stable, particularly if they contain proline residues, because they cannot form perfect β-bridges in the FG regions that link the swapped dimers. The Tencon β-swapped variants with the longest FG sequences are observed to form higher order hexameric or helical oligomeric structures in the crystal correlating well with the aggregation properties of these domains observed in solution. Understanding the structural basis for domain-swapped dimerization and oligomerization will support engineering efforts of the Tencon domain to produce variants with desired biophysical properties.

PubMed: 24375666
DOI: 10.1002/prot.24502

実験手法

X-RAY DIFFRACTION (1.92 Å)