PDBsum entry 5cfh

Immune system

PDB id: 5cfh

Contents

Protein chain

99 a.a.

Waters ×141

PDB id:

5cfh

Name:

Immune system

Title:

Human beta-2 microglobulin double mutant w60g-y63w

Structure:

Beta-2-microglobulin. Chain: a. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: b2m, cdabp0092, hdcma22p. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.49Å R-factor: 0.172 R-free: 0.230

Authors:

B.M.Sala,M.De Rosa,M.Bolognesi,S.Ricagno

Key ref:

C.Camilloni et al. (2016). Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability. Sci Rep, 6, 25559. PubMed id: 27150430 DOI: 10.1038/srep25559

Date:

08-Jul-15 Release date: 18-May-16

Protein chain

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

Seq: 119 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/srep25559

Sci Rep 6:25559 (2016)

PubMed id: 27150430

Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability.

C.Camilloni, B.M.Sala, P.Sormanni, R.Porcari, A.Corazza, M.De Rosa, S.Zanini, A.Barbiroli, G.Esposito, M.Bolognesi, V.Bellotti, M.Vendruscolo, S.Ricagno.

ABSTRACT

A wide range of human diseases is associated with mutations that, destabilizing proteins native state, promote their aggregation. However, the mechanisms leading from folded to aggregated states are still incompletely understood. To investigate these mechanisms, we used a combination of NMR spectroscopy and molecular dynamics simulations to compare the native state dynamics of Beta-2 microglobulin (β2m), whose aggregation is associated with dialysis-related amyloidosis, and its aggregation-resistant mutant W60G. Our results indicate that W60G low aggregation propensity can be explained, beyond its higher stability, by an increased average protection of the aggregation-prone residues at its surface. To validate these findings, we designed β2m variants that alter the aggregation-prone exposed surface of wild-type and W60G β2m modifying their aggregation propensity. These results allowed us to pinpoint the role of dynamics in β2m aggregation and to provide a new strategy to tune protein aggregation by modulating the exposure of aggregation-prone residues.