PDBsum entry 3ekc

Immune system

PDB id

3ekc

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Contents

			Protein chain

					100 a.a. *

			Waters ×124

* Residue conservation analysis

PDB id:

3ekc

Links

Name:

Immune system

Title:

Structure of w60v beta-2 microglobulin mutant

Structure:

Beta-2-microglobulin. Chain: a. Synonym: beta-2-microglobulin form pi 5.3. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nm_004048. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å

R-factor:

0.187

R-free:

0.241

Authors:

S.Ricagno,E.Sangiovanni,V.Bellotti,M.Bolognesi

Key ref:

S.Ricagno et al. (2009). Human beta-2 microglobulin W60V mutant structure: Implications for stability and amyloid aggregation. Biochem Biophys Res Commun, 380, 543-547. PubMed id: 19284997

Date:

19-Sep-08

Release date:

26-May-09

PROCHECK

	Headers

	References

Protein chain

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

Seq: Struc:					119 a.a. 100 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

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

	Biochem Biophys Res Commun 380:543-547 (2009)
PubMed id: 19284997

Human beta-2 microglobulin W60V mutant structure: Implications for stability and amyloid aggregation.
S.Ricagno, S.Raimondi, S.Giorgetti, V.Bellotti, M.Bolognesi.

ABSTRACT

Beta-2 microglobulin (?2m) is the light chain of class I major histocompatibility complex (MHC-I). Beta2m is an intrinsically amyloidogenic protein that can assemble into amyloid fibrils in a concentration dependent manner. Beta2m is accumulated in serum of haemodialysed patients, and deposited in the skeletal joints, causing dialysis related amyloidosis. Recent reports suggested that the loop comprised between beta2m strands D and E is crucial for protein stability and for beta2m propensity to aggregate as cross-beta structured fibrils. In particular, the role of Trp60 for beta2m stability has been highlighted by showing that the Trp60-->Gly beta2m mutant is more thermo-stable and less prone to aggregation than the wild type protein. On the contrary the Asp59-->Pro beta2m mutant shows lower Tm and stronger tendency to fibril aggregation. To further analyse such properties, the Trp60-->Val beta2m mutant has been expressed and purified; the propensity to fibrillar aggregation and the folding stability have been assessed, and the X-ray crystal structure determined to 1.8A resolution. The W60V mutant structural features are discussed, focusing on the roles of the DE loop and of residue 60 in relation to ?2m structure and its amyloid aggregation trends.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20506535

C.Santambrogio, S.Ricagno, M.Colombo, A.Barbiroli, F.Bonomi, V.Bellotti, M.Bolognesi, and R.Grandori (2010).
DE-loop mutations affect beta2 microglobulin stability, oligomerization, and the low-pH unfolded form.

Protein Sci, 19, 1386-1394.

19393661

K.E.Routledge, G.G.Tartaglia, G.W.Platt, M.Vendruscolo, and S.E.Radford (2009).
Competition between intramolecular and intermolecular interactions in an amyloid-forming protein.

J Mol Biol, 389, 776-786.

19657763

N.H.Heegaard (2009).
beta(2)-microglobulin: from physiology to amyloidosis.

Amyloid, 16, 151-173.

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.