4KDT

Structure of an early native-like intermediate of beta2-microglobulin amyloidosis

Summary for 4KDT

• Entry DOI: 10.2210/pdb4kdt/pdb
• Descriptor: Nanobody24, Beta-2-microglobulin, SULFATE ION, ... (5 entities in total)
• Functional Keywords: immunoglobulin fold, immune system
• Biological source: Camelidae; More
• Cellular location: Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 4
• Total formula weight: 54422.11

Authors

Vanderhaegen, S.,Fislage, M.,Pardon, E.,Versees, W.,Steyaert, J. (deposition date: 2013-04-25, release date: 2013-08-28, Last modification date: 2024-11-20)

Primary citation

Vanderhaegen, S.,Fislage, M.,Domanska, K.,Versees, W.,Pardon, E.,Bellotti, V.,Steyaert, J.
Structure of an early native-like intermediate of beta 2-microglobulin amyloidogenesis.
Protein Sci., 22:1349-1357, 2013

PubMed Abstract: To investigate early intermediates of β2-microglobulin (β2m) amyloidogenesis, we solved the structure of β2m containing the amyloidogenic Pro32Gly mutation by X-ray crystallography. One nanobody (Nb24) that efficiently blocks fibril elongation was used as a chaperone to co-crystallize the Pro32Gly β2m monomer under physiological conditions. The complex of P32G β2m with Nb24 reveals a trans peptide bond at position 32 of this amyloidogenic variant, whereas Pro32 adopts the cis conformation in the wild-type monomer, indicating that the cis to trans isomerization at Pro32 plays a critical role in the early onset of β2m amyloid formation.

PubMed: 23904325
DOI: 10.1002/pro.2321

Experimental method

X-RAY DIFFRACTION (2.6 Å)