PDBsum entry 1soq

Transport protein

PDB id

1soq

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Contents

			Protein chain

					116 a.a. *

			Waters ×157

* Residue conservation analysis

PDB id:

1soq

Links

Name:

Transport protein

Title:

Crystal structure of the transthyretin mutant a108y/l110e solved in space group c2

Structure:

Transthyretin. Chain: a, b, c, d. Synonym: prealbumin, tbpa, ttr, attr. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ttr, palb. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.10Å

R-factor:

0.212

R-free:

0.246

Authors:

A.Hornberg,A.Olofsson,T.Eneqvist,E.Lundgren,A.E.Sauer-Eriksson

Key ref:

A.Hörnberg et al. (2004). The beta-strand D of transthyretin trapped in two discrete conformations. Biochim Biophys Acta, 1700, 93. PubMed id: 15210129 DOI: 10.1016/j.bbapap.2004.04.004

Date:

15-Mar-04

Release date:

06-Jul-04

PROCHECK

	Headers

	References

Protein chains

P02766 (TTHY_HUMAN) - Transthyretin from Homo sapiens

Seq: Struc:					147 a.a. 116 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.bbapap.2004.04.004	Biochim Biophys Acta 1700:93 (2004)
PubMed id: 15210129

The beta-strand D of transthyretin trapped in two discrete conformations.
A.Hörnberg, A.Olofsson, T.Eneqvist, E.Lundgren, A.E.Sauer-Eriksson.

ABSTRACT

Conformational changes in native and variant forms of the human plasma protein transthyretin (TTR) induce several types of amyloid diseases. Biochemical and structural studies have mapped the initiation site of amyloid formation onto residues at the outer C and D beta-strands and their connecting loop. In this study, we characterise an engineered variant of transthyretin, Ala108Tyr/Leu110Glu, which is kinetically and thermodynamically more stable than wild-type transthyretin, and as a consequence less amyloidogenic. Crystal structures of the mutant were determined in two space groups, P2(1)2(1)2 and C2, from crystals grown in the same crystallisation set-up. The structures are identical with the exception for residues Leu55-Leu58, situated at beta-strand D and the following DE loop. In particular, residues Leu55-His56 display large shifts in the C2 structure. There the direct hydrogen bonding between beta-strands D and A has been disrupted and is absent, whereas the beta-strand D is present in the P2(1)2(1)2 structure. This difference shows that from a mixture of metastable TTR molecules, only the molecules with an intact beta-strand D are selected for crystal growth in space group P2(1)2(1)2. The packing of TTR molecules in the C2 crystal form and in the previously determined amyloid TTR (ATTR) Leu55Pro crystal structure is close-to-identical. This packing arrangement is therefore not unique in amyloidogenic mutants of TTR.

Literature references that cite this PDB file's key reference

PubMed id

Reference

19088715

F.Chiti, and C.M.Dobson (2009).
Amyloid formation by globular proteins under native conditions.

Nat Chem Biol, 5, 15-22.

16627944

E.Morais-de-Sá, R.M.Neto-Silva, P.J.Pereira, M.J.Saraiva, and A.M.Damas (2006).
The binding of 2,4-dinitrophenol to wild-type and amyloidogenic transthyretin.

Acta Crystallogr D Biol Crystallogr, 62, 512-519.

PDB codes:

2b14 2b15 2b16

16219761

C.A.Keetch, E.H.Bromley, M.G.McCammon, N.Wang, J.Christodoulou, and C.V.Robinson (2005).
L55P transthyretin accelerates subunit exchange and leads to rapid formation of hybrid tetramers.

J Biol Chem, 280, 41667-41674.

15821170

M.Yang, M.Lei, R.Bruschweiler, and S.Huo (2005).
Initial conformational changes of human transthyretin under partially denaturing conditions.

Biophys J, 89, 433-443.

16204882

P.Neumann, V.Cody, and A.Wojtczak (2005).
Ligand binding at the transthyretin dimer-dimer interface: structure of the transthyretin-T4Ac complex at 2.2 Angstrom resolution.

Acta Crystallogr D Biol Crystallogr, 61, 1313-1319.

PDB code:

1z7j

15469931

E.Morais-de-Sá, P.J.Pereira, M.J.Saraiva, and A.M.Damas (2004).
The crystal structure of transthyretin in complex with diethylstilbestrol: a promising template for the design of amyloid inhibitors.

J Biol Chem, 279, 53483-53490.

PDB codes:

1tt6 1tz8

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.