Metal Ion Binding Properties and Conformational States of Calcium- and Integrin-Binding Protein

Yamniuk, Aaron P.; Nguyen, Leonard T.; Hoang, Tung T.; Vogel, Hans J.

doi:10.1021/bi035432b

Cited by 78 publications

(131 citation statements)

References 53 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…Ca 2ϩ induces a conformational change in CIB1 (17) and modulates the binding and regulatory actions of CIB1 on several CIB1-interacting proteins (18,30). In the present study, the binding of CIB1 to ASK1 was blocked either by ionomycin (Fig.…”

Section: Discussionsupporting

confidence: 48%

“…Although it was initially discovered in platelets as a protein that interacts with integrin ␣ IIb (11), CIB1 also binds many other proteins including presenilin 2, DNA-dependent protein kinase, the polo-like kinases Fnk and Snk (14)(15)(16). Furthermore, the binding of Ca 2ϩ to CIB1 induces conformational changes that modulate the interaction with at least some of its binding proteins (17). CIB1 is widely expressed among tissues (18) and is likely to play a role in various cellular processes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

Yoon¹,

Cho²,

Lee³

et al. 2009

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

View full text Add to dashboard Cite

Calcium and integrin binding protein 1 (CIB1) is a Ca 2+ -binding protein of 22 kDa that was initially identified as a protein that interacts with integrin α IIb . Although it interacts with various proteins and has been implicated in diverse cellular functions, the molecular mechanism by which CIB1 regulates intracellular signaling networks has remained unclear. We now show that, by targeting apoptosis signal-regulating kinase 1 (ASK1), CIB1 negatively regulates stress-activated MAPK signaling pathways. CIB1 was thus shown to bind to ASK1, to interfere with the recruitment of TRAF2 to ASK1, and to inhibit the autophosphorylation of ASK1 on threonine-838, thereby blocking ASK1 activation. Furthermore, CIB1 mitigated apoptotic cell death initiated either by TNF-α in breast cancer MCF7 cells or by 6-hydroxydopamine (6-OHDA) in dopaminergic cells. Ca 2+ influx induced by membrane depolarization reversed the inhibitory effect of CIB1 on 6-OHDA-induced ASK1 activation and cell death in dopaminergic neurons. These observations thus suggest that CIB1 functions as a Ca 2+ -sensitive negative regulator of ASK1-mediated signaling events.

show abstract

Section: Discussionsupporting

confidence: 48%

mentioning

confidence: 99%

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

Yoon¹,

Cho²,

Lee³

et al. 2009

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

View full text Add to dashboard Cite

show abstract

“…Sample Preparation-The CIB1 protein was prepared as described previously (17). The 13 C, 2 H, 15 N-uniformly labeled sample was expressed and purified according to an established protocol (12), and this sample was used to acquire the backbone 1 7 -glucose; this sample was used to record the CIB1 backbone CPMG-relaxation dispersion spectra.…”

Section: Methodsmentioning

confidence: 99%

“…Because the magnesium ion is constantly present in the cytosol in millimolar concentrations, the magnesium-bound form of CIB1 (Mg 2ϩ -CIB1) is considered to be the physiologically relevant form of CIB1 in the resting state of the cell (17). CIB1 has been found to bind Mg 2ϩ only at its EF-III site, but it still possesses an overall well folded tertiary structure (17 ther suggested that Mg 2ϩ -CIB1 and Ca 2ϩ -CIB1 have similar tertiary structures with subtle differences (18).…”

mentioning

confidence: 99%

“…CIB1 has been found to bind Mg 2ϩ only at its EF-III site, but it still possesses an overall well folded tertiary structure (17 ther suggested that Mg 2ϩ -CIB1 and Ca 2ϩ -CIB1 have similar tertiary structures with subtle differences (18). In addition, as both Ca 2ϩ -CIB1 and Mg 2ϩ -CIB1 can bind to ␣IIb with similar binding affinities, the role of CIB1 for being a specific Ca 2ϩ sensor has been brought into question (10).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Solution Structures of Ca2+-CIB1 and Mg2+-CIB1 and Their Interactions with the Platelet Integrin αIIb Cytoplasmic Domain

Huang

Ishida

Yamniuk

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The calcium-and integrin-binding protein 1 (CIB1) is a ubiquitous Ca 2؉ -binding protein and a specific binding partner for the platelet integrin ␣IIb cytoplasmic domain, which confers the key role of CIB1 in hemostasis. CIB1 is also known to be involved in apoptosis, embryogenesis, and the DNA damage response. In this study, the solution structures of both Ca 2؉ -CIB1 and Mg 2؉ -CIB1 were determined using solution-state NMR spectroscopy. The methyl groups of Ile, Leu, and Val were selectively protonated to compensate for the loss of protons due to deuteration. The solution structure of Ca 2؉ -CIB1 possesses smaller opened EF-hands in its C-domain compared with available crystal structures. Ca 2؉ -CIB1 and Mg 2؉ -CIB1 have similar structures, but the N-lobe of Mg 2؉ -CIB1 is slightly more opened than that of Ca 2؉ -CIB1. Additional NMR experiments, such as chemical shift perturbation and methyl group solvent accessibility as measured by a nitroxide surface probe, were carried out to further characterize the structures of Ca 2؉ -CIB1 and Mg 2؉ -CIB1 as well as their interactions with the integrin ␣IIb cytoplasmic domain. NMR measurements of backbone amide proton slow motion (microsecond to millisecond) dynamics confirmed that the C-terminal helix of Ca 2؉ -CIB1 is displaced upon ␣IIb binding. The EF-hand III of both Ca 2؉ -CIB1 and Mg 2؉ -CIB1 was identified to be directly involved in the interaction of CIB1 with ␣IIb. Together, these data illustrate that CIB1 behaves quite differently from related EF-hand regulatory calcium-binding proteins, such as calmodulin or neuronal calcium sensor proteins.The calcium-and integrin-binding protein 1 (CIB1) is a member of the regulatory Ca 2ϩ -binding helix-loop-helix or EFhand protein family (1). CIB1 is a ubiquitous 191-residue (22 kDa) protein with several functions in cell signaling (2, 3). CIB1 has been reported to interact with a number of protein targets, including the platelet integrin ␣IIb subunit (4), sphingosine kinase 1 (5), p21-activated kinase (6), apoptosis signal-regulating kinase (7), polo-like protein kinases (8), and a recently reported new target in the regulation of cardiac hypertrophy, calcineurin B (9). The interaction of CIB1 with the integrin ␣IIb subunit has been studied extensively (10 -13). The integrin ␣IIb subunit usually associates with the integrin ␤3 subunit, and the heterodimeric ␣IIb␤3 protein is involved in both so-called "inside-out" and "outside-in" signaling pathways (3). CIB1 is believed to be capable of specifically binding to the ␣IIb cytoplasmic domain and dissociating the ␣IIb␤3 dimer, which in turn triggers integrin activation (11,12). The interactions between Ca 2ϩ -CIB1 and a fragment of the integrin ␣IIb subunit (residues 983-1008, hereafter referred to as the ␣IIb peptide) have been suggested to mainly involve a hydrophobic pocket in the C-domain of Ca 2ϩ -CIB1 with a dissociation constant in the submicromolar range (10).The calcium-bound CIB1 (Ca 2ϩ -CIB1) structure consists of four helix-loop-helix (EF-hand) Ca 2ϩ -binding m...

show abstract

Circular Dichroism ( CD ) Spectroscopy

Presta¹,

Stillman²

2005

Encyclopedia of Inorganic Chemistry

View full text Add to dashboard Cite

Circular dichroism (CD) spectroscopy is of fundamental importance as a tool in all areas of chemistry and biochemistry because this technique is the simplest and fastest measure of the presence of the chiral species that lead to optical activity. Chiral centers and chiral species exist from the simplest molecules to complex organic molecules, from inorganic complexes to metal‐based biological molecules, typically metalloproteins; from folded polymers, which are typically peptides and proteins; to the supramolecular organization of the quaternary structure of proteins; including all forms of helical structure typified by the the double helix; to liquid crystals and beyond, to even more massive and organized species. For all these species, CD spectroscopy provides insight into the presence and the extent of the chiral electric field induced by the atomic and molecular organization. The optical activity is detected under electronic and vibrational absorption bands as a result of the differential absorption of left‐ and right‐circularly polarized light. Measurement of mirror images of the CD spectrum is commonly used to determine the enantiomeric purity of small molecules. The measurement of the change, and sometimes loss, of optical activity measured in the spectral region of the chiral chromophores can be used to determine and understand the denaturation of a folded protein as the chirality changes with the change in gross structural features associated with the folding. We focus particularly in this chapter on the influence of metals on the chiral properties of proteins. Metal binding results in changes in molecular and supramolecular conformations readily measured under metal‐based spectral bands. In cases for which the folding of the protein is almost entirely metal‐induced, the CD spectrum becomes an extremely sensitive marker for structural change as a function of metal loading allowing both the stoichiometry of metal binding and the coordination geometry to be proposed. Measurement of the chirality of a molecule is easy in the region 190–1000 nm as several relatively inexpensive instruments provide high sensitivity. Time‐resolved CD spectral data are also readily achievable using stopped‐flow devices. Measurement in the infrared regions is also popular and provides invaluable information; instruments can now be purchased “off the shelf”. The new growth area is the use of synchrotron radiation as the light source allowing CD spectral data to be measured in all regions of the electromagnetic spectrum, but particularly, for energies higher than 50 000 cm −1 (below 200 nm).

show abstract

Metal Ion Binding Properties and Conformational States of Calcium- and Integrin-Binding Protein

Cited by 78 publications

References 53 publications

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

Solution Structures of Ca2+-CIB1 and Mg2+-CIB1 and Their Interactions with the Platelet Integrin αIIb Cytoplasmic Domain

Circular Dichroism ( CD ) Spectroscopy

Contact Info

Product

Resources

About

Metal Ion Binding Properties and Conformational States of Calcium- and Integrin-Binding Protein

Cited by 78 publications

References 53 publications

CIB1 functions as a Ca 2+ -sensitive modulator of stress-induced signaling by targeting ASK1

CIB1 functions as a Ca 2+ -sensitive modulator of stress-induced signaling by targeting ASK1

Solution Structures of Ca2+-CIB1 and Mg2+-CIB1 and Their Interactions with the Platelet Integrin αIIb Cytoplasmic Domain

Circular Dichroism ( CD ) Spectroscopy

Contact Info

Product

Resources

About

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1