Troponin T is capable of binding dystrophin via a leucine zipper

Pearlman, Joel; Powaser, Peter A.; Elledge, Stephen J.; Caskey, C. Thomas

doi:10.1016/0014-5793(94)01119-2

Cited by 19 publications

(13 citation statements)

References 26 publications

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“…Hence, the role of the HR motif in TnT-TnI binary interaction has not been established prior to this study. Recently, it was reported that fast skeletal TnT binds to dystrophin by coiled coil-or leucine zipper-mediated interaction (29). However, the in vivo relevance of this finding is not clear, and the authors also did not investigate what region of TnT was involved in the interaction with dystrophin.…”

Section: Discussionmentioning

confidence: 52%

Identification and mutagenesis of a highly conserved domain in troponin T responsible for troponin I binding: Potential role for coiled coil interaction

Stefancsik

Jha

Sarkar

1998

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

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Troponin T (TnT), a thin filament myofibrillar protein, is essential for the Ca 2؉ regulation of striated muscle contraction in vertebrates, both in vivo and in vitro. To understand the role of TnT in this process, its interaction with two other troponin components, troponin I (TnI) and troponin C (TnC) was examined by using the yeast two hybrid system, which is a genetic approach to detect protein-protein interactions. Computer assisted analysis of phylogenetically distant TnT amino acid sequences unveiled a highly conserved protein domain that is characterized by a heptad repeat (HR) motif with a potential for ␣-helical coiled coil formation. A similar, potentially coiled coil forming domain is also conserved in all known TnI sequences. These protein motifs appeared to be the regions where TnI-TnT interaction may take place. Deletions and point mutations in TnT, which disrupted its HR motif, severely reduced or abolished TnI binding, but binding to TnC was not affected, indicating that the TnT-TnI and TnT-TnC binary interactions can be uncoupled. Remarkably, the truncated fragments of TnT and TnI in which the HR motifs were retained showed binary interaction in the yeast two hybrid system. It was also observed that the formation of the TnT-TnI heterodimers is favored over the homodimers TnT-TnT and TnI-TnI. These results indicate that the evolutionarily conserved HR motifs may play a role in TnT-TnI dimerization, presumably through the formation of ␣-helical coiled coils.

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Section: Discussionmentioning

confidence: 52%

Identification and mutagenesis of a highly conserved domain in troponin T responsible for troponin I binding: Potential role for coiled coil interaction

Stefancsik

Jha

Sarkar

1998

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

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“…However, anity absorption is not mediated by a classical leucine zipper interaction. Leucine zipper domains play a well-documented role in facilitating homodimer and heterodimer formation with many dierent proteins, including transcription factors (Hurst, 1994), cellular kinases (Ruth et al, 1997;Gamm et al, 1995;Kitigawa et al, 1995), transmembrane receptors (Saras et al, 1994;Klein et al, 1993;Rodrigues and Park, 1993;Chen et al, 1993;Earl et al, 1993) and cytoskeletal proteins (Klein et al, 1993;Bikle et al, 1996;Pearlman et al, 1994;Ward and Kirshner, 1990;Maekawa and Kuriyama, 1993). The mechanism for dimer formation by leucine zippers requires hydrophobic interactions between opposing leucine residues in the heptad repeats, which may be stabilized by charge interactions (Hodges, 1992).…”

Section: Discussionmentioning

confidence: 99%

Src can regulate carboxy terminal interactions with AFAP-110, which influence self-association, cell localization and actin filament integrity

et al. 1998

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The SH2 and SH3 binding partner AFAP-110 is a tyrosine phosphorylated substrate of Src. AFAP-110 has been hypothesized to link Src to actin ®laments, which may contribute to the eects of Src upon actin ®lament integrity. However, it has been unclear what eect activated Src (Src 527F ) has upon AFAP-110 structure or function and whether AFAP-110 plays a role in actin ®lament integrity. We report here that the carboxy terminal 127 amino acids of AFAP-110 are comprised of an a-helical region that contains a leucine zipper motif. This indicated the potential of AFAP-110 to selfassociate. Expression of the carboxy terminus as a fusion protein (GST-cterm) will permit anity absorption of cellular AFAP-110. The integrity of the a-helical leucine zipper motif in GST-cterm is required for anity absorption, but binding is not due to a classical leucine zipper interaction. Co-expression of Src 527F , unlike cSrc, will abrogate anity absorption of AFAP-110 with GST-cterm. These data indicate that Src 527F has aected a change in the carboxy terminal structure that renders AFAP-110 unavailable for anity absorption. Superose chromatography demonstrate that AFAP-110 will fractionate as a monomer or multimer, indicating AFAP-110 can be detected in a selfassociated form in cell lysates. Co-expression of Src 527F resulted in AFAP-110 fractionating with a molecular weight that predicts only a multimeric population. Deletional mutagenesis also indicate a biological role for the carboxy terminus in cellular localization and actin ®lament integrity. Deletion of the entire carboxy terminal a-helix (84 amino acids) will not permit AFAP-110 to eciently colocalize with actin ®laments or the cell membrane. Deletion of only the leucine zipper region of the carboxy terminal a-helix (44 amino acids) from AFAP-110 (AFAPA Dzip ) demonstrate that both AFAP Dlzip and actin ®laments are repositioned into rosette-like structures, similar to the eects of Src 527F , while co-expression of AFAP-110 with cSrc will not aect actin ®laments. These data indicate that AFAP-110 can play an important role in modulating actin ®lament integrity through carboxy terminal interactions that can be aected by Src .

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“…A 91-bp-long residue sequence that includes two sequences corresponding to structures referred to as the "leucine zippers," which are typical of several gene regulatory proteins (33,34), is located between the coiled-coil region and the collagenous stretch. This finding is rather unusual especially for an ECM protein, as there are only a few precedents in the literature for the presence of leucine zippers in the extra nuclear compartments: the Drosophila ECM protein pollux (35) and the cytoplasmic protein dystrophin, whose leucine zipper has been reported to interact with troponin (36). Although the leucine zipper pattern is far from being specific, it is not clear at the moment what might be the significance of its presence in the context of EMILIN.…”

Section: Purification and Peptide Sequences Of Chick Emilin-amentioning

confidence: 95%

EMILIN, a Component of the Elastic Fiber and a New Member of the C1q/Tumor Necrosis Factor Superfamily of Proteins

Doliana

Mongiat

Bucciotti

et al. 1999

Journal of Biological Chemistry

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EMILIN (elastin microfibril interface located protein)is an extracellular matrix glycoprotein abundantly expressed in elastin-rich tissues such as blood vessels, skin, heart, and lung. It occurs associated with elastic fibers at the interface between amorphous elastin and microfibrils. Avian EMILIN was extracted from 19-dayold embryonic chick aortas and associated blood vessels and purified by ion-exchange chromatography and gel filtration. Tryptic peptides were generated from EMI-LIN and sequenced, and degenerate inosine-containing oligonucleotide primers were designed from some peptides. A set of primers allowed the amplification of a 360-base pair reverse transcription polymerase chain reaction product from chick aorta mRNA. A probe based on a human homologue selected by comparison of the chick sequence with EST data base was used to select overlapping clones from both human aorta and kidney cDNA libraries. Here we present the cDNA sequence of the entire coding region of human EMILIN encompassing an open reading frame of 1016 amino acid residues. There was a high degree of homology (76% identity and 88% similarity) between the chick C terminus and the human sequence as well as between the N terminus of the mature chick protein where 10 of 12 residues, as determined by N-terminal sequencing, were identical or similar to the deduced N terminus of human EMILIN. The domain organization of human EMILIN includes a C1q-like globular domain at the C terminus, a collagenous stalk, and a longer segment in which at least four heptad repeats and a leucine zipper can be identified with a high potential for forming coiled-coil ␣ helices. At the N terminus there is a cysteine-rich sequence stretch similar to a region of multimerin, a platelet and endothelial cell component, containing a partial epidermal growth factor-like motif. The native state of the recombinantly expressed EMILIN C1q-like domain to be used in cell adhesion was determined by CD spectra analysis, which indicated a high value of ␤-sheet conformation. The EMILIN C1q-like domain promoted a high cell adhesion of the leiomyosarcoma cell line SK-UT-1, whereas the fibrosarcoma cell line HT1080 was negative.

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Troponin T is capable of binding dystrophin via a leucine zipper

Cited by 19 publications

References 26 publications

Identification and mutagenesis of a highly conserved domain in troponin T responsible for troponin I binding: Potential role for coiled coil interaction

Identification and mutagenesis of a highly conserved domain in troponin T responsible for troponin I binding: Potential role for coiled coil interaction

Src can regulate carboxy terminal interactions with AFAP-110, which influence self-association, cell localization and actin filament integrity

EMILIN, a Component of the Elastic Fiber and a New Member of the C1q/Tumor Necrosis Factor Superfamily of Proteins

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