4KDT

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

PDB DOI: https://doi.org/10.2210/pdb4KDT/pdb

Classification: IMMUNE SYSTEM
Organism(s): Camelidae, Homo sapiens
Expression System: Escherichia coli, Escherichia coli BL21(DE3)
Mutation(s): Yes

Deposited: 2013-04-25 Released: 2013-08-28
Deposition Author(s): Vanderhaegen, S., Fislage, M., Pardon, E., Versees, W., Steyaert, J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.274
R-Value Work: 0.226
R-Value Observed: 0.228

wwPDB Validation 3D Report Full Report

This is version 1.3 of the entry. See complete history.

Literature

Structure of an early native-like intermediate of beta 2-microglobulin amyloidogenesis.

Vanderhaegen, S., Fislage, M., Domanska, K., Versees, W., Pardon, E., Bellotti, V., Steyaert, J.

(2013) Protein Sci 22: 1349-1357

PubMed: 23904325 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1002/pro.2321
Primary Citation of Related Structures:
4KDT

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.

Organizational Affiliation

Structural Biology Research Centre, VIB, Pleinlaan 2, 1050, Brussel, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussel, Belgium.

Macromolecule Content

Total Structure Weight: 54.42 kDa
Atom Count: 3,679
Modelled Residue Count: 445
Deposited Residue Count: 468
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Nanobody24	A, B	134	Camelidae	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Beta-2-microglobulin	C, D	100	Homo sapiens	Mutation(s): 1 Gene Names: B2M, CDABP0092, HDCMA22P
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens) Explore P61769 Go to UniProtKB: P61769
PHAROS: P61769 GTEx: ENSG00000166710
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P61769
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth B] SDF format, chain I [auth C] SDF format, chain K [auth D] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth B] MOL2 format, chain I [auth C] MOL2 format, chain K [auth D]	E [auth A] F [auth A] G [auth A] H [auth B] I [auth C] E [auth A], F [auth A], G [auth A], H [auth B], I [auth C], K [auth D]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth B] Focus chain I [auth C] Focus chain K [auth D] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth B] Focus chain I [auth C] Focus chain K [auth D]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain J [auth C] SDF format, chain L [auth D] MOL2 format, chain J [auth C] MOL2 format, chain L [auth D]	J [auth C], L [auth D]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain J [auth C] Focus chain L [auth D] Interactions & Density Focus chain J [auth C] Focus chain L [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.274
R-Value Work: 0.226
R-Value Observed: 0.228
Space Group: P 4₂ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 96.79	α = 90
b = 96.79	β = 90
c = 167.79	γ = 90

Software Package:

Software Name	Purpose
PHASER	phasing
REFMAC	refinement
XDS	data reduction
XDS	data scaling

Structure Validation

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Entry History

Deposition Data

Released Date: 2013-08-28

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2013-08-28
Type: Initial release
Version 1.1: 2013-10-23
Changes: Database references
Version 1.2: 2017-11-15
Changes: Refinement description
Version 1.3: 2023-09-20
Changes: Data collection, Database references, Derived calculations, Refinement description