1ICT

MONOCLINIC FORM OF HUMAN TRANSTHYRETIN COMPLEXED WITH THYROXINE (T4)

1ICT の概要

• エントリーDOI: 10.2210/pdb1ict/pdb
• 関連するPDBエントリー: 1TTA 2PAB 2ROX
• 分子名称: TRANSTHYRETIN, 3,5,3',5'-TETRAIODO-L-THYRONINE (2 entities in total)
• 機能のキーワード: albumin, transport, amyloid, thyroid hormone, liver, plasma, polyneuropathy, thyroxine, prealbumin, greek key beta barrel, transport protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P02766
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 111772.62

構造登録者

Wojtczak, A.,Neumann, P.,Cody, V. (登録日: 2001-04-02, 公開日: 2002-04-03, 最終更新日: 2023-11-15)

主引用文献

Wojtczak, A.,Neumann, P.,Cody, V.
Structure of a new polymorphic monoclinic form of human transthyretin at 3 A resolution reveals a mixed complex between unliganded and T4-bound tetramers of TTR.
Acta Crystallogr.,Sect.D, 57:957-967, 2001

PubMed Abstract: The crystal structure of a new polymorphic form of human transthyretin (hTTR) with a lattice containing a unique assembly of apo hTTR and TTR-T(4) complex has been determined to 3 A resolution. The monoclinic form of human TTR reported here crystallizes in space group P2(1), with unit-cell parameters a = 76.7 (6), b = 96.7 (8), c = 81.7 (4) A, beta = 106.8 (4) degrees. The asymmetric unit contains two tetramers of transthyretin related by the non-crystallographic symmetry (NCS) operation of a 90.28 degrees rotation between two hTTR molecules around an axis close to crystallographic z. The r.m.s. difference between the two tetramers calculated from their C(alpha) positions is 0.48 A. The structure was refined using 15.0-3.0 A resolution data to R = 22.9% and R(free) = 28.9% for reflections F > 0.0sigma(F), and R = 19.7% and R(free) = 25.8% for reflections F > 3.0sigma(F). The intermolecular interactions involve the tips of alpha-helices and loops around Arg21, Glu61 and Ser100 of all monomers. The electron-density maps revealed residual thyroxine (T(4)) bound in only one of the two unique tetrameric TTR molecules, with an occupancy of 53%, while the second tetramer is unliganded. One thyroxine ligand is bound in a way similar to the orientations described for the orthorhombic form of the hTTR-T(4) complex. The T(4) bound in the second site is positioned similar to 3',5'-dinitro-N-acetyl-L-thyronine in its hTTR complex. Differences in the size of the central channel defined by the D, A, G and H beta-strands of two monomeric subunits are observed between the apo TTR and T(4)-bound tetramer. The averaged distances between Ala108 C(alpha) and its equivalent measured across each binding site are 12.34 A for the T(4)-bound and 10.96 A for the unliganded TTR tetramer, respectively. The observed differences might reflect the mechanics of the ligand binding in the channel and possibly explain the observed negative cooperativity effect for ligand binding.

PubMed: 11418763
DOI: 10.1107/S0907444901006047

実験手法

X-RAY DIFFRACTION (3 Å)