TY - JOUR
T1 - Pathological self-aggregation of β2-microglobulin
T2 - A challenge for protein biophysics
AU - Esposito, Gennaro
AU - Corazza, Alessandra
AU - Bellotti, Vittorio
N1 - Publisher Copyright:
© 2012 Springer Science+Business Media Dordrecht.
PY - 2012/5/29
Y1 - 2012/5/29
N2 - The pathological aggregation of β2-microglobulin (β2m) is examined starting from the relevance of some structural aspects of the protein. The systemic deposition of β2m fibrils has been ascribed to several factors, but no conclusive evidence emerged so far. The characterization of β2m aggregates by direct investigation through electron microscopy, atomic force microscopy, solid state NMR and other solid state techniques provides important structural and morphological information on the assembly, but no clues about the mechanism of the aggregation process. The most relevant mechanistic hypotheses are critically reviewed. In addition to the mechanisms exclusively based on structural features, also the recently reported prion-like conversion is analyzed and shown to hardly comply with some established conditions of the fibrillogenic process. An alternative mechanism is recalled that does not require rare events and involves only the full-length protein in proximity of collagen, i.e. the environment that physiologically supports deposition.
AB - The pathological aggregation of β2-microglobulin (β2m) is examined starting from the relevance of some structural aspects of the protein. The systemic deposition of β2m fibrils has been ascribed to several factors, but no conclusive evidence emerged so far. The characterization of β2m aggregates by direct investigation through electron microscopy, atomic force microscopy, solid state NMR and other solid state techniques provides important structural and morphological information on the assembly, but no clues about the mechanism of the aggregation process. The most relevant mechanistic hypotheses are critically reviewed. In addition to the mechanisms exclusively based on structural features, also the recently reported prion-like conversion is analyzed and shown to hardly comply with some established conditions of the fibrillogenic process. An alternative mechanism is recalled that does not require rare events and involves only the full-length protein in proximity of collagen, i.e. the environment that physiologically supports deposition.
KW - Aggregation
KW - β2-Microglobulin (β2m)
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U2 - 10.1007/978-94-007-5416-4_7
DO - 10.1007/978-94-007-5416-4_7
M3 - Article
C2 - 23225003
AN - SCOPUS:84894446315
SN - 0306-0225
VL - 65
SP - 165
EP - 183
JO - Subcellular Biochemistry
JF - Subcellular Biochemistry
ER -