1jnj

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NMR solution structure of the human beta2-microglobulin

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The solution structure of human beta2-microglobulin (beta2-m), the, nonpolymorphic component of class I major histocompatibility complex, (MHC-I), was determined by (1)H NMR spectroscopy and restrained modeling, calculations. Compared to previous structural data obtained from the NMR, secondary structure of the isolated protein and the crystal structure of, MHC-I, in which the protein is associated to the heavy-chain component, several differences are observed. The most important rearrangements were, observed for (1) strands V and VI (loss of the C-terminal and N-terminal, end, respectively), (2) interstrand loop V-VI, and (3) strand I, including, the N-terminal segment (displacement outward of the molecular core). These, modifications can be considered as the prodromes of the amyloid, transition. Solvation of the protected regions in MHC-I decreases the, tertiary packing by breaking the contiguity of the surface hydrophobic, patches at the interface with heavy chain and the nearby region at the, surface charge cluster of the C-terminal segment. As a result, the, molecule is placed in a state in which even minor charge and solvation, changes in response to pH or ionic-strength variations can easily, compromise the hydrophobic/hydrophilic balance and trigger the transition, into a partially unfolded intermediate that starts with unpairing of, strand I and leads to polymerization and precipitation into fibrils or, amorphous aggregates. The same mechanism accounts for the partial, unfolding and fiber formation subsequent to Cu(2+) binding, which is shown, to occur primarily at His 31 and involve partially also His 13, the next, available His residue along the partial unfolding pathway.

Disease

Known disease associated with this structure: Hypoproteinemia, hypercatabolic OMIM:[109700]

About this Structure

1JNJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The solution structure of human beta2-microglobulin reveals the prodromes of its amyloid transition., Verdone G, Corazza A, Viglino P, Pettirossi F, Giorgetti S, Mangione P, Andreola A, Stoppini M, Bellotti V, Esposito G, Protein Sci. 2002 Mar;11(3):487-99. PMID:11847272

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