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PDBsum entry 1py4
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Signaling protein
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PDB id
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1py4
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Beta2-Microglobulin h31y variant 3d structure highlights the protein natural propensity towards intermolecular aggregation.
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Authors
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C.Rosano,
S.Zuccotti,
P.Mangione,
S.Giorgetti,
V.Bellotti,
F.Pettirossi,
A.Corazza,
P.Viglino,
G.Esposito,
M.Bolognesi.
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Ref.
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J Mol Biol, 2004,
335,
1051-1064.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2004,
335,
1051-1064)
copyright 2004.
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