New partner proteins containing novel internal recognition motif for human glutaminase interacting protein (hGIP)

Zencir, Sevil; Banerjee, Monimoy; Dobson, Melanie J.; Ayaydin, Ferhan; Fodor, Elfrieda; Topçu, Zeki; Mohanty, Smita

doi:10.1016/j.bbrc.2013.01.098

Cited by 7 publications

(8 citation statements)

References 34 publications

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“…TIP-1 belongs to the Class I PDZ domain family that recognizes proteins containing an X-S/T-X-I/L/V-COOH C-terminal recognition motif. The list of proteins now known to be recognized by TIP-1 through their C-terminal motif has been steadily growing [ 16 , 32 , 33 , 34 , 35 ]. These interacting partners are involved in various biological functions such as cell proliferation, stress response, development and cell polarization [ 36 , 37 , 38 ], implicating the role of TIP-1 in the regulation of these processes.…”

Section: The Pdz Domain Of Tip-1mentioning

confidence: 99%

PDZ Domain Recognition: Insight from Human Tax-Interacting Protein 1 (TIP-1) Interaction with Target Proteins

Mohanty

Ovee

Banerjee

2015

Biology

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Cellular signaling is primarily directed via protein-protein interactions. PDZ (PSD-95/Discs large/ZO-1 homologous) domains are well known protein-protein interaction modules involved in various key signaling pathways. Human Tax-interacting protein 1 (TIP-1), also known as glutaminase interaction protein (GIP), is a Class I PDZ domain protein that recognizes the consensus binding motif X-S/T-X-V/I/L-COOH of the C-terminus of its target proteins. We recently reported that TIP-1 not only interacts via the C-terminus of its target partner proteins but also recognizes an internal motif defined by the consensus sequence S/T-X-V/L-D in the target protein. Identification of new target partners containing either a C-terminal or internal recognition motif has rapidly expanded the TIP-1 protein interaction network. TIP-1 being composed solely of a single PDZ domain is unique among PDZ containing proteins. Since it is involved in many important signaling pathways, it is a possible target for drug design. In this mini review, we have discussed human TIP-1, its structure, mechanism of function, its interactions with target proteins containing different recognition motifs, and its involvement in human diseases. Understanding the molecular mechanisms of TIP-1 interactions with distinct target partners and their role in human diseases will be useful for designing novel therapeutics.

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Section: The Pdz Domain Of Tip-1mentioning

confidence: 99%

PDZ Domain Recognition: Insight from Human Tax-Interacting Protein 1 (TIP-1) Interaction with Target Proteins

Mohanty

Ovee

Banerjee

2015

Biology

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“…Some of the well-studied PDZ domains whose structures are available in PDB, e.g. Par-6 10 , DVL2 11 , DLG1-1 and hGIP [12][13] can recognize both C-terminal and internal peptides by utilizing conformational plasticity of their carboxylate-binding loop.…”

Section: Introductionmentioning

confidence: 99%

Structural basis of internal peptide recognition by PDZ domains using molecular dynamics simulations

Sain

Mohanty

2019

Preprint

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PDZ domains are important peptide recognition modules which usually recognize short C-terminal stretches of their interaction partners, but certain PDZ domains can also recognize internal peptides in the interacting proteins. Due to the scarcity of data on internal peptide recognition and lack of understanding of the mechanistic details of internal peptide recognition, identification of PDZ domains capable of recognizing internal peptides has been a difficult task.Since Par-6 PDZ domain can recognize both C-terminal and internal peptides, we have carried out multiple explicit solvent MD simulations of 1 μs duration on free and peptide bound Par-6 PDZ to decipher mechanistic details of internal peptide recognition. These simulations have been analyzed to identify residues which play a crucial role in internal peptide recognition by PDZ domains. Based on the conservation profile of the identified residues, we have predicted 47 human PDZ domains to be capable of recognizing internal peptides in human. We have also investigated how binding of CDC42 to the CRIB domain adjacent to the Par6 PDZ allosterically modulate the peptide recognition by Par6 PDZ. Our MD simulations on CRIB-Par6_PDZ didomain in isolation as well as in complex with CDC42, indicate that in absence of CDC42 the adjacent CRIB domain induces open loop conformation of PDZ facilitating internal peptide recognition. On the other hand, upon binding of CDC42 to the CRIB domain, Par6 PDZ adopts closed loop conformation required for recognition of C-terminus peptides. These results provide atomistic details of how binding of interaction partners onto adjacent domains can allosterically regulate substrate binding to PDZ domains. In summary, MD simulations provide novel insights into the modulation of substrate recognition preference of PDZ by specific peptides, adjacent domains and binding of interaction partners at allosteric sites.

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“…20,21 Both of these metals are neurotoxic 22 and affect glutamate signaling, leading to a variety of brain disorders including the above-mentioned diseases. 23 Since TIP1 plays a vital role in numerous signaling pathways including glutamate, Wnt, Rho, and potassium channel Kir, 11,16,[24][25][26] it is of great interest to understand the effect of metals on TIP1 structure, which in turn can interfere with its function. Here, we report the effect of arsenic and cadmium on the structure of TIP1 using circular dichroism (CD) and fluorescence spectroscopy techniques.…”

mentioning

confidence: 99%

“…[33][34][35] Human TIP1 is involved in various signaling pathways controlling key biological processes including regulation of the cerebral concentration of neurotransmitter glutamate, β-catenin-mediated Wnt signaling, Rho-activator Rhotekin, and potassium channel Kir2.3 signaling pathway. 11,16,[24][25][26]36 Considering the importance of TIP1 for the well-being of a living cell, it is of great importance to investigate the effect of toxic metals on the structure of TIP1 and consequently on its function below levels that are currently allowed. We report here the effects of two metals, arsenic and cadmium, on TIP1 structure/conformation.…”

mentioning

confidence: 99%

Effect of Toxic Metal Binding on Tax-Interacting Protein1 (TIP1): A Protein Related to Brain Diseases

Chaudhary

Dahal

Sayania

et al. 2019

Natural Product Communications

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Human tax-interacting protein1 (TIP1), also known as glutaminase-interacting protein (GIP), is a small globular protein containing a PDZ domain. PDZ domains are the most common protein-protein interaction modules present in eukaryotes. In humans, TIP1 plays a very important role in many cellular pathways including β-catenin-mediated Wnt signaling, Rhoactivator rhotekin-mediated Rho signaling pathway, and glutamate signaling pathway for the normal activity of the central nervous system. TIP1 also regulates potassium channel expression in the plasma membrane and is a binding partner to many proteins including viral oncoproteins, HTLV-1 Tax and HPV16 E6. Since TIP1 is at a pivotal point in many cellular processes through its interaction with a growing list of partner proteins, any impact on the proper functioning of this protein can have severe consequences on the well-being of a living system. Although metals are essential for plants and animals in trace amounts, elevated levels of heavy metals such as arsenic, cadmium, zinc, and lead are toxic causing various health problems including cardiovascular disorders, neuronal damage, renal injuries, and cancer. Here, we report the effect of heavy metals, arsenic and cadmium, on TIP1 conformation using circular dichroism and fluorescence spectroscopy techniques. Our study revealed these metals have a significant impact on the structure of TIP1 even at very low levels.

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New partner proteins containing novel internal recognition motif for human glutaminase interacting protein (hGIP)

Cited by 7 publications

References 34 publications

PDZ Domain Recognition: Insight from Human Tax-Interacting Protein 1 (TIP-1) Interaction with Target Proteins

PDZ Domain Recognition: Insight from Human Tax-Interacting Protein 1 (TIP-1) Interaction with Target Proteins

Structural basis of internal peptide recognition by PDZ domains using molecular dynamics simulations

Effect of Toxic Metal Binding on Tax-Interacting Protein1 (TIP1): A Protein Related to Brain Diseases

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