PDBsum entry 1py4

Signaling protein

PDB id: 1py4

Contents

Protein chains

98 a.a. *

Waters ×30

* Residue conservation analysis

PDB id:

1py4

Name:

Signaling protein

Title:

Beta2 microglobulin mutant h31y displays hints for amyloid formations

Structure:

Beta-2-microglobulin precursor. Chain: a, b, c, d. Fragment: h31y. Synonym: hdcma22p. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: b2m. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.90Å R-factor: 0.241 R-free: 0.313

Authors:

C.Rosano,S.Zuccotti,P.Mangione,S.Giorgetti,V.Bellotti,F.Pettirossi, A.Corazza,P.Viglino,G.Esposito,M.Bolognesi

Key ref:

C.Rosano et al. (2004). beta2-microglobulin H31Y variant 3D structure highlights the protein natural propensity towards intermolecular aggregation. J Mol Biol, 335, 1051-1064. PubMed id: 14698299 DOI: 10.1016/j.jmb.2003.11.040

Date:

08-Jul-03 Release date: 04-May-04

Protein chains

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

Seq: 119 a.a.

Struc: 98 a.a.*

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

DOI no: 10.1016/j.jmb.2003.11.040

J Mol Biol 335:1051-1064 (2004)

PubMed id: 14698299

beta2-microglobulin H31Y variant 3D structure highlights the protein natural propensity towards intermolecular aggregation.

C.Rosano, S.Zuccotti, P.Mangione, S.Giorgetti, V.Bellotti, F.Pettirossi, A.Corazza, P.Viglino, G.Esposito, M.Bolognesi.

ABSTRACT

beta2-Microglobulin (beta2m) is the non-covalently bound light chain of the human class I major histocompatibility complex (MHC-I). The natural turnover of MHC-I gives rise to the release of beta2m into plasmatic fluids and to its catabolism in the kidney. beta2m dissociation from the heavy chain of the complex is a severe complication in patients receiving prolonged hemodialysis. As a consequence of renal failure, the increasing beta2m concentrations can lead to deposition of the protein as amyloid fibrils. Here we characterize the His31-->Tyr human beta2m mutant, a non-natural form of beta2m that is more stable than the wild-type protein, displaying a ten-fold acceleration of the slow phase of folding. We report the 2.9A resolution crystal structure and the NMR characterization of the mutant beta2m, focussing on selected structural features and on the molecular packing observed in the crystals. Juxtaposition of the four mutant beta2m molecules contained in the crystal asymmetric unit, and specific hydrogen bonds, stabilize a compact protein assembly. Conformational heterogeneity of the four independent molecules, some of their mutual interactions and partial unpairing of the N-terminal beta-strand in one protomer are in keeping with the amyloidogenic properties displayed by the mutant beta2m.

Selected figure(s)

Figure 2.
Figure 2. (A) A structural comparison of the protein fold in H31Yb2m independent chains, A (green) and C (red) chains; (B) structural comparison of H31Yb2m A chain (green) and monomeric human wild-type b2m (blue); in this orientation, the different conformation adopted by the A-B loop, in the two proteins, is particularly evident.

Figure 4.
Figure 4. A mono view of the eight-stranded b-sheet resulting from the antiparallel pairing of two D2 b-strands provided by the A and D asymmetric unit independent chains. The two b-bulges at Asp53 (red residues) are evident in the centre of the Figure, dividing the D1 b-strand (grey worm) and the D2 b-strand (green ribbon).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 335, 1051-1064) copyright 2004.

Figures were selected by an automated process.