4PVM

Neutron structure of human transthyretin (TTR) at room temperature to 2.0A resolution (Laue)

Summary for 4PVM

• Entry DOI: 10.2210/pdb4pvm/pdb
• Related: 2PAB 3IPE 3U2I 4PVL 4PVN
• Descriptor: Transthyretin (2 entities in total)
• Functional Keywords: beta sandwich, transport protein, serum
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P02766
• Total number of polymer chains: 2
• Total formula weight: 28073.38

Authors

Fisher, S.J.,Blakeley, M.P.,Haupt, M.,Mason, S.A.,Cooper, J.B.,Mitchell, E.P.,Forsyth, V.T. (deposition date: 2014-03-18, release date: 2014-11-12, Last modification date: 2024-03-20)

Primary citation

Haupt, M.,Blakeley, M.P.,Fisher, S.J.,Mason, S.A.,Cooper, J.B.,Mitchell, E.P.,Forsyth, V.T.
Binding site asymmetry in human transthyretin: insights from a joint neutron and X-ray crystallographic analysis using perdeuterated protein
IUCrJ, 1:429-438, 2014

PubMed Abstract: Human transthyretin has an intrinsic tendency to form amyloid fibrils and is heavily implicated in senile systemic amyloidosis. Here, detailed neutron structural studies of perdeuterated transthyretin are described. The analyses, which fully exploit the enhanced visibility of isotopically replaced hydrogen atoms, yield new information on the stability of the protein and the possible mechanisms of amyloid formation. Residue Ser117 may play a pivotal role in that a single water molecule is closely associated with the γ-hydrogen atoms in one of the binding pockets, and could be important in determining which of the two sites is available to the substrate. The hydrogen-bond network at the monomer-monomer interface is more extensive than that at the dimer-dimer interface. Additionally, the edge strands of the primary dimer are seen to be favourable for continuation of the β-sheet and the formation of an extended cross-β structure through sequential dimer couplings. It is argued that the precursor to fibril formation is the dimeric form of the protein.

PubMed: 25485123
DOI: 10.1107/S2052252514021113

Experimental method

NEUTRON DIFFRACTION (2 Å)
X-RAY DIFFRACTION (1.95 Å)