PDBsum entry 4x0s

Immune system

PDB id: 4x0s

Contents

Protein chain

16 a.a.

Ligands

SO4

Metals

_NA

_CL

PDB id:

4x0s

Name:

Immune system

Title:

Hexamer formed by a macrocycle containing a sequence from beta-2- microglobulin (63-69).

Structure:

Orn-tyr-leu-leu-phi-tyr-val-glu-orn-lys-val-ala-maa-ala- val-lys. Chain: a. Engineered: yes

Source:

Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Other_details: derived from beta-2-microglobulin 63-69

Resolution:

2.03Å R-factor: 0.168 R-free: 0.202

Authors:

R.K.Spencer,P.J.Salveson,J.S.Nowick

Key ref:

R.K.Spencer et al. (2015). X-ray Crystallographic Structures of Oligomers of Peptides Derived from β2-Microglobulin. J Am Chem Soc, 137, 6304-6311. PubMed id: 25915729 DOI: 10.1021/jacs.5b01673

Date:

23-Nov-14 Release date: 06-May-15

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 16 a.a.*

* PDB and UniProt seqs differ at 11 residue positions (black crosses)

DOI no: 10.1021/jacs.5b01673

J Am Chem Soc 137:6304-6311 (2015)

PubMed id: 25915729

X-ray Crystallographic Structures of Oligomers of Peptides Derived from β2-Microglobulin.

R.K.Spencer, A.G.Kreutzer, P.J.Salveson, H.Li, J.S.Nowick.

ABSTRACT

Amyloid diseases such as Alzheimer's disease, Parkinson's disease, and type II diabetes share common features of toxic soluble protein oligomers. There are no structures at atomic resolution of oligomers formed by full-length amyloidogenic peptides and proteins, and only a few structures of oligomers formed by peptide fragments. The paucity of structural information provides a fundamental roadblock to understanding the pathology of amyloid diseases and developing preventions or therapies. Here, we present the X-ray crystallographic structures of three families of oligomers formed by macrocyclic peptides containing a heptapeptide sequence derived from the amyloidogenic E chain of β2-microglobulin (β2m). Each macrocyclic peptide contains the heptapeptide sequence β2m63-69 and a second heptapeptide sequence containing an N-methyl amino acid. These peptides form β-sheets that further associate into hexamers, octamers, and dodecamers: the hexamers are trimers of dimers; the octamers are tetramers of dimers; and the dodecamers contain two trimer subunits surrounded by three pairs of β-sheets. These structures illustrate a common theme in which dimer and trimer subunits further associate to form a hydrophobic core. The seven X-ray crystallographic structures not only illustrate a range of oligomers that a single amyloidogenic peptide sequence can form, but also how mutation can alter the size and topology of the oligomers. A cocrystallization experiment in which a dodecamer-forming peptide recruits a hexamer-forming peptide to form mixed dodecamers demonstrates that one species can dictate the oligomerization of another. These findings should also be relevant to the formation of oligomers of full-length peptides and proteins in amyloid diseases.