The structure of a Ca2+-binding epidermal growth factor-like domain: Its role in protein-protein interactions

Rao, Zihe; Handford, Penny A.; Mayhew, Mark; Knott, Vroni; Brownlee, George G.; Stuart, D.I.

doi:10.1016/0092-8674(95)90059-4

Cited by 344 publications

(288 citation statements)

References 56 publications

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“…Third, given mounting evidence that acidic residue clusters can bind calcium specifically [27,33,34], several candidate calcium-binding sites are evident in the globally acidic (pI 4.8) Fl-~-subunit. Most notable is a highly conserved superficial loop of the Fl-~-subunit that contains the acidic sequence DELSEED, is known to bind cationic inhibitors, and is not mirrored in the basic (theoretical pI 8.8) Fl-c~-subunit [19,32,35].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

1996

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Mitochondrial ATP synthase is responsive to changes in cytosolic calcium concentration, but the regulatory mechanisms are unclear. Here we identified a major 52 kDa calciumbinding protein in rat enamel cells as the mitochondrial ATP synthase Fl-~subunit. The Fl-~-subunit behaved as a low affinity and moderate capacity calcium-binding protein during comparative 45Ca overlay analyses. Equivalent behavior was shown by the Fl-[I-subunit from rat liver mitochondria, but not by the homologous Fl-a-subunit, supporting the specificity of calcium binding. Evidence that the catalytic Fr~-subuuit binds calcium specifically introduces new mechanistic possibilities for regulating ATP synthase, and thereby coordinating ATP production with demand for ATP-fuelled calcium pump activity.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

1996

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“…The functional consequences of calcium binding to proteins containing this structural element are not yet known, but it was suggested that calcium may stabilize the structure of fibrillin-1 in a rod-like arrangement (38) and may protect the molecule from proteolytic degradation (39). The crystal structure of human clotting factor IX which shows a calcium-binding EGF-like domain suggests that calcium may be involved in maintaining the conformation of the N-terminal region of the domain but, more importantly, proves that calcium is able to directly mediate protein-protein interactions (40). The Sushi domain of VCP and the calcium binding EGFlike domain of fibrillin-1 require a specific internal arrangement of the numerous disulfide bonds that we used to model the membrane proximal TPO region.…”

Section: Resultsmentioning

confidence: 99%

Molecular Model, Calcium Sensitivity, and Disease Specificity of a Conformational Thyroperoxidase B-cell Epitope

Estienne¹,

Blanchet²,

Niccoli-Sire³

et al. 1999

Journal of Biological Chemistry

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While studying the humoral mechanisms involved in thyroid autoimmunity, we located a B-cell autoepitope in the extracellular C-terminal region of human thyroperoxidase. Structural modeling showed that this region encompasses both a Sushi-like and an epidermal growth factor-like domain, the flexible arrangement of which was putatively stabilized by calcium. The recombinant peptide was found to contain the previously identified conformational thyroperoxidase autoepitope. The occurrence of a calcium-induced conformational change was confirmed using a recombinant peptide monoclonal antibody, the decrease of which in binding to calcium-saturated thyroperoxidase was reversed by a chelating agent. The disease specificity of recombinant peptide, which was more frequently recognized by Hashimoto's than by Graves' patients, adds to its potential value as a diagnostic and preventive tool in the context of B-cell autoimmunity. Thyroperoxidase (TPO)1 plays a key role in the biosynthesis of thyroid hormones by catalyzing both the iodination of tyrosine residues and the coupling of some iodotyrosine residues in thyroglobulin to form tri-and tetraiodothyronines. It is a hemecontaining membrane enzyme which is expressed at the apical pole of thyrocytes facing the colloid space (1). TPO belongs to the mammalian peroxidase family, the members of which include myelo-, lacto-, eosinophil, and salivary peroxidases (2). Human TPO contains 933 amino acids (aa), and shows a large extracellular region consisting of 848 aa and five potential glycosylation sites, a short membrane-spanning region, and a 61-aa cytoplasmic tail. Most of the extracellular region of TPO shows a high degree of homology with myeloperoxidase (aa 1-739). The extracellular region close to the membrane anchorage domain shows homologies with the C4b complement component (aa 739 -794) and EGF (aa 794 -842) (3). The threedimensional structure of TPO is not yet known, and elucidating this point constitutes an important task for scientists investigating the peroxidase family and for immunologists focusing on autoimmunity questions because TPO is a major thyroid autoantigen.Autoantibodies (aAb) to TPO are the most sensitive and specific serological markers available for diagnosing autoimmune thyroid diseases. Like most antibodies to exogenous antigens, TPO aAb are produced by B lymphocytes via a T-celldependent mechanism involving specific cellular receptors and soluble cytokines. At the molecular level, however, the specificity of the autoimmune reaction relies on the recognition of TPO epitopes by T and B-cells (4). T-cell receptors recognize linear epitopes from processed TPO associated with class II molecules belonging to the major histocompatibility complex, which are co-expressed at the surface of antigen-presenting cells. By contrast, B-cell receptors, which are membrane-bound immunoglobulins, usually have a more stringent specificity and recognize conformational epitopes, i.e. they are highly dependent on the three-dimensional structure of the TPO molecule (5-7).

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“…4A and Dataset S1). These domains are known from other studies to mediate protein-protein, protein-carbohydrate, or protein-metal interactions (22)(23)(24)(25) and could therefore provide cohesive and adhesive interactions between Sfp1 and other glycans and/or proteins present in the adhesive material and in the outermost layer of the tube foot cuticle, respectively (14,16,19). To the best of our knowledge, the only other marine adhesive proteins presenting such conserved functional domains are the mussel proteins mussel foot protein 2 (mfp-2), with 11 repeats of EGF-like domains (26,27), and proximal thread matrix protein 1 (Ptmp-1), with two von Willebrand factor type A domains (28).…”

Section: Resultsmentioning

confidence: 99%

Sea star tenacity mediated by a protein that fragments, then aggregates

Hennebert

Wattiez

Demeuldre

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

101

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Sea stars adhere firmly but temporarily to various substrata as a result of underwater efficient adhesive secretions released by their tube feet. Previous studies showed that this material is mainly made up of proteins, which play a key role in its adhesiveness and cohesiveness. Recently, we solubilized the majority of these proteins and obtained 43 de novo-generated peptide sequences by tandem MS. Here, one of these sequences served to recover the full-length sequence of Sea star footprint protein 1 (Sfp1), by RT-PCR and tube foot transcriptome analysis. Sfp1, a large protein of 3,853 aa, is the second most abundant constituent of the secreted adhesive. By using MS and Western blot analyses, we showed that Sfp1 is translated from a single mRNA and then cleaved into four subunits linked together by disulphide bridges in tube foot adhesive cells. The four subunits display specific protein-, carbohydrate-, and metal-binding domains. Immunohistochemistry and immunocytochemistry located Sfp1 in granules stockpiled by one of the two types of adhesive cells responsible for the secretion of the adhesive material. We also demonstrated that Sfp1 makes up the structural scaffold of the adhesive footprint that remains on the substratum after tube foot detachment. Taken together, the results suggest that Sfp1 is a major structural protein involved in footprint cohesion and possibly in adhesive interactions with the tube foot surface. In recombinant form, it could be used for the design of novel sea starinspired biomaterials.echinoderms | Asterias rubens | marine adhesion

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The structure of a Ca2+-binding epidermal growth factor-like domain: Its role in protein-protein interactions

Cited by 344 publications

References 56 publications

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

Molecular Model, Calcium Sensitivity, and Disease Specificity of a Conformational Thyroperoxidase B-cell Epitope

Sea star tenacity mediated by a protein that fragments, then aggregates

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The structure of a Ca2+-binding epidermal growth factor-like domain: Its role in protein-protein interactions

Cited by 344 publications

References 56 publications

Mitochondrial ATP synthase F1‐β‐subunit is a calcium‐binding protein

Mitochondrial ATP synthase F1‐β‐subunit is a calcium‐binding protein

Molecular Model, Calcium Sensitivity, and Disease Specificity of a Conformational Thyroperoxidase B-cell Epitope

Sea star tenacity mediated by a protein that fragments, then aggregates

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Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein