The N-terminal domain of βb2-crystallin resembles the putative ancestral homodimer

Clout, Naomi J.; Basak, A.K.; Wieligmann, Karin; Bateman, O.A.; Jaenicke, Rainer; Slingsby, C.

doi:10.1006/jmbi.2000.4197

Cited by 25 publications

(24 citation statements)

References 23 publications

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“…The other two families, the ␤-and ␥-crystallins (4 -6), are evolutionary related structural proteins that have close to 30% sequence identity and similar polypeptide chain folds. The double Greek key motif characteristic of their structures has been found to occur in microbial stress proteins (7,8). Subunits of ␤-crystallins assemble into dimers and higher oligomers, whereas ␥-crystallins are monomeric.…”

mentioning

confidence: 99%

Binding of Destabilized βB2-Crystallin Mutants to α-Crystallin

Sathish

Koteiche

Mchaourab

2004

Journal of Biological Chemistry

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Age-related changes in protein-protein interactions in the lens play a critical role in the temporal evolution of its optical properties. In the relatively non-regenerating environment of the fiber cells, a critical determinant of these interactions is partial or global unfolding as a consequence of post-translational modifications or chemical damage to individual crystallins. One type of attractive force involves the recognition by ␣-crystallins of modified proteins prone to unfolding and aggregation. In this paper, we explore the energetic threshold and the structural determinants for the formation of a stable complex between ␣-crystallin and ␤B2-crystallin as a consequence of destabilizing mutations in the latter. The mutations were designed in the framework of a folding model that proposes the equilibrium population of a monomeric intermediate. Binding to ␣-crystallin is detected through changes in the emission properties of a bimane fluorescent probe site-specifically introduced at a solvent exposed site in ␤B2-crystallin. ␣-Crystallin binds the various ␤B2-crystallin mutants, although with a significantly lower affinity relative to destabilized T4 lysozyme mutants. The extent of binding, while reflective of the overall destabilization, is determined by the dynamic population of a folding intermediate. The existence of the intermediate is inferred from the biphasic bimane emission unfolding curve of a mutant designed to disrupt interactions at the dimer interface. The results of this paper are consistent with a model in which the interaction of ␣-crystallins with substrates is not solely triggered by an energetic threshold but also by the population of excited states even under favorable folding conditions. The ability of ␣-crystallin to detect subtle changes in the population of ␤B2-crystallin excited states supports a central role for this chaperone in delaying aggregation and scattering in the lens.In the inner regions of the lens, transparency and refractivity are dependent on the stability, high solubility, and packing of three families of proteins, collectively referred to as crystallins (1-3). One of these families, the ␣-crystallins, consists of two small heat-shock proteins (sHSP) that can recognize and bind non-native states of proteins. The other two families, the ␤-and ␥-crystallins (4 -6), are evolutionary related structural proteins that have close to 30% sequence identity and similar polypeptide chain folds. The double Greek key motif characteristic of their structures has been found to occur in microbial stress proteins (7,8). Subunits of ␤-crystallins assemble into dimers and higher oligomers, whereas ␥-crystallins are monomeric.The ␤-crystallin family of the vertebrate lens consists of six distinct gene products that segregate into two classes, basic and acidic (9). Despite extensive sequence similarity, one of the hallmarks that distinguish members of the two classes is Nand C-terminal extensions of variable lengths, the age-related truncation of which adds another dimension of molecular ...

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confidence: 99%

Binding of Destabilized βB2-Crystallin Mutants to α-Crystallin

Sathish

Koteiche

Mchaourab

2004

Journal of Biological Chemistry

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“…Comparison of the dimeric structures of vertebrate [βB2-crystallin, Protein Data Bank (PDB) ID 1E7N] 19 and microbial (spherulin 3a, PDB ID 1HDF) βγ-crystallin domains reveals the presence of an interface exclusive to nitrollin among all βγ-crystallins (Fig. 8b and c).…”

Section: Discussionmentioning

confidence: 93%

“…19 In nitrollin, Leu72 replaces tyrosine residue (Fig. 1b), which remains unexposed to the solvent due to the presence of the swapped strand and forms part of the hydrophobic core of the swapped dimer (Fig.…”

Section: Loop Docking In the Dimeric Interfacementioning

confidence: 99%

“…17,18 Truncated single domains of γ-and β-crystallins associate to form dimers in solution. 19,20 β-Crystallins exist as dimers or tetramers due to associations mediated by terminal extensions and domain swapping. [21][22][23] Dimers of βB2-crystallin associate by completely swapping one of their domains with their partner and form an intermolecular interface similar to that of the monomeric γ-crystallin, in which the same interface is formed with intramolecular associations among the two domains.…”

Section: Introductionmentioning

confidence: 99%

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Three-Dimensional Domain Swapping in Nitrollin, a Single-Domain βγ-Crystallin from Nitrosospira multiformis, Controls Protein Conformation and Stability but Not Dimerization

Penmatsa

Suman

Mishra

et al. 2009

Journal of Molecular Biology

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“…For completeness, we also include in Table 2 two reports not covered by the reviews (Croall and Demartino, 1991;Goll et al, 2003). These data pertain to the m-calpain cleavage of N-terminal propeptides of b-crystallin, which are highly mobile and in random coil conformations (PDB: 1E7N; Clout et al, 2000).…”

Section: Bereitgestellt Von | Universitaetsbibliothek Der Lmu Muenchenmentioning

confidence: 99%

Proteolysis of insulin-like growth factor binding proteins (IGFBPs) by calpain

Ghosh

Shanker

Siwanowicz

et al. 2005

Biological Chemistry

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Calpains are non-lysosomal, Ca 2q -dependent cysteine proteases, which are ubiquitously distributed across cell types and vertebrate species. The rules that govern calpain specificity have not yet been determined. To elucidate the cleavage pattern of calpains, we carried out calpain-induced proteolytic studies on the insulin-like growth factor binding proteins IGFBP-4 and -5. Proteolysis of IGFBPs is well characterized in numerous reports. Our results show that calpain cleavage sites are in the non-conserved unstructured regions of the IGFBPs. Compilation of the calpain-induced proteolytic cleavage sites in several proteins reported in the literature, together with our present study, has not revealed clear preferences for amino acid sequences. We therefore conclude that calpains seem not to recognize amino acid sequences, but instead cleave with low sequence specificity at unstructured or solvent-exposed fragments that connect folded, stable domains of target proteins.

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The N-terminal domain of βb2-crystallin resembles the putative ancestral homodimer

Cited by 25 publications

References 23 publications

Binding of Destabilized βB2-Crystallin Mutants to α-Crystallin

Binding of Destabilized βB2-Crystallin Mutants to α-Crystallin

Three-Dimensional Domain Swapping in Nitrollin, a Single-Domain βγ-Crystallin from Nitrosospira multiformis, Controls Protein Conformation and Stability but Not Dimerization

Proteolysis of insulin-like growth factor binding proteins (IGFBPs) by calpain

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