scholarly journals Dimerization of ubiquilin is dependent upon the central region of the protein: evidence that the monomer, but not the dimer, is involved in binding presenilins

2006 ◽  
Vol 399 (3) ◽  
pp. 397-404 ◽  
Author(s):  
Diana L. Ford ◽  
Mervyn J. Monteiro
Keyword(s):  
Central Region ◽  
Regulatory Mechanism ◽  
Active Form ◽  
Cellular Proteins ◽  
Interacting Protein ◽  
C Terminus ◽  
N Terminus ◽  
The Stability ◽  
Insight Into

Ubiquilin proteins have been shown to interact with a wide variety of other cellular proteins, often regulating the stability and degradation of the interacting protein. Ubiquilin contains a UBL (ubiquitin-like) domain at the N-terminus and a UBA (ubiquitin-associated) domain at the C-terminus, separated by a central region containing Sti1-like repeats. Little is known about regulation of the interaction of ubiquilin with other proteins. In the present study, we show that ubiquilin is capable of forming dimers, and that dimerization requires the central region of ubiquilin, but not its UBL or the UBA domains. Furthermore, we provide evidence suggesting that monomeric ubiquilin is likely to be the active form that is involved in binding presenilin proteins. Our results provide new insight into the regulatory mechanism underlying the interaction of ubiquilin with presenilins.

Degradation of ornithine decarboxylase: exposure of the C-terminal target by a polyamine-inducible inhibitory protein

1993 ◽  
Vol 13 (4) ◽  
pp. 2377-2383
Author(s):  
X Li ◽  
P Coffino
Keyword(s):  
Conformational Change ◽  
Ornithine Decarboxylase ◽  
Binding Protein ◽  
Active Form ◽  
Feedback Regulation ◽  
Degradation Process ◽  
Protein Inhibitor ◽  
Inhibitory Protein ◽  
C Terminus ◽  
N Terminus

Polyamine-mediated degradation of vertebrate ornithine decarboxylase (ODC) is associated with the production of antizyme, a reversible tightly binding protein inhibitor of ODC activity. The interaction of antizyme with a binding element near the N terminus of ODC is essential but not sufficient for regulation of the enzyme by polyamines (X. Li and P. Coffino, Mol. Cell. Biol. 12:3556-2562, 1992). We now show that a second element present at the C terminus is required for the degradation process. Antizyme caused a conformational change in ODC, which made the C terminus of ODC more accessible. Blocking the C terminus with antibody prevented degradation. Tethering the C terminus by creating a circularly permuted, enzymatically active form of ODC prevented antizyme-mediated degradation. These data elucidate a form of feedback regulation whereby excess polyamines induce destruction of ODC, the enzyme that initiates their biosynthesis.

scholarly journals An mDia1-INF2 formin activation cascade facilitated by IQGAP1 regulates stable microtubules in migrating cells

2016 ◽  
Vol 27 (11) ◽  
pp. 1797-1808 ◽  
Author(s):  
Francesca Bartolini ◽  
Laura Andres-Delgado ◽  
Xiaoyi Qu ◽  
Sara Nik ◽  
Nagendran Ramalingam ◽  
...  
Keyword(s):  
Lysophosphatidic Acid ◽  
Dependent Manner ◽  
Common Pathway ◽  
Interacting Protein ◽  
C Terminus ◽  
N Terminus ◽  
In Series ◽  
Activation Cascade ◽  
Unique Mechanism ◽  
Migrating Cells

Multiple formins regulate microtubule (MT) arrays, but whether they function individually or in a common pathway is unknown. Lysophosphatidic acid (LPA) stimulates the formation of stabilized detyrosinated MTs (Glu MTs) in NIH3T3 fibroblasts through RhoA and the formin mDia1. Here we show that another formin, INF2, is necessary for mDia1-mediated induction of Glu MTs and regulation of MT dynamics and that mDia1 can be bypassed by activating INF2. INF2 localized to MTs after LPA treatment in an mDia1-dependent manner, suggesting that mDia1 regulates INF2. Mutants of either formin that disrupt their interaction failed to rescue MT stability in cells depleted of the respective formin, and the mDia1-interacting protein IQGAP1 regulated INF2’s localization to MTs and the induction of Glu MTs by either formin. The N-terminus of IQGAP1 associated with the C-terminus of INF2 directly, suggesting the possibility of a tripartite complex stimulated by LPA. Supporting this, the interaction of mDia1 and INF2 was induced by LPA and dependent on IQGAP1. Our data highlight a unique mechanism of formin action in which mDia1 and INF2 function in series to stabilize MTs and point to IQGAP1 as a scaffold that facilitates the activation of one formin by another.

scholarly journals The interplay of the type II TA system with other processes

2019 ◽  
Author(s):  
Wei Wen-ping ◽  
Jia Wan Zhong ◽  
Yang Min
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Environmental Stress ◽  
Regulatory Mechanism ◽  
Phage Infection ◽  
Type Ii ◽  
System Research ◽  
Cellular Processes ◽  
The Stability ◽  
And Function ◽  
Insight Into

The type II toxin antitoxin (TA) system is the most well-studied TA system and is widely distributed in bacteria, especially pathogens such as Mycobacterium tuberculosis. Type II TA system plays an important role in many cellular processes, including maintaining the stability of mobile genetic elements, and bacterial altruistic suicide in response to nutritional starvation, environmental stress and phage infection. Interactions between toxin proteins and antitoxin proteins are critical for the regulation and function of type II TA systems; indeed, the understanding of their function is mainly derived from interaction and regulation of paired TA system proteins. Nonetheless, investigating interaction between unpaired TA system proteins, and the interaction between TA system proteins and other functional proteins, are becoming more common and have provided new insight into the complexity of its regulatory mechanism. In this review, we outlined the cross-interaction between TA system proteins, and the interaction between TA system proteins and other functional proteins, and we are trying to explain novel mechanism of TA system in the regulation of cellular activities. On this basis, we further discussed the knowledge and physiological implications of the relevant aspects of TA system research.

The Stability of Wild-type and Deletion Mutants of Human C-terminus Hsp70-interacting Protein (CHIP)

2013 ◽  
Vol 20 (5) ◽  
pp. 524-529 ◽  
Author(s):  
Isabel C.R. Millan ◽  
Ana L.A. Squillace ◽  
Lisandra M. Gava ◽  
Carlos H.I. Ramos
Keyword(s):  
Protein Chip ◽  
Deletion Mutants ◽  
Wild Type ◽  
Interacting Protein ◽  
C Terminus ◽  
The Stability

Molecular Modeling and Virtual Screening of Molecular Inhibitors for Leptospiral Collagenase

2021 ◽  
Author(s):  
Vikram Kumar ◽  
Nagesh Srikaku ◽  
Veeranarayanan Surya Aathmanathan ◽  
Padikara K Satheeshkumar ◽  
Madanan Gopalakrishnan Madathiparambil ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Modeling ◽  
Active Site ◽  
Binding Sites ◽  
Catalytic Site ◽  
Simulation Studies ◽  
C Terminus ◽  
Ligand Binding Sites ◽  
N Terminus ◽  
The Stability

Abstract Collagenase is a virulence factor which facilitates the invasion of pathogenic Leptospira into the host. In the present study, the model of Leptopsiral collagenase was constructed by employing threading method with the crystal structure of collagenase G. Three ligand binding sites at N- terminus, catalytic site and C-terminus were predicted by Metapocket server. Among sixty seven inhibitors from the ChEBI and Zinc databases, Protohypericin is predicted as the best inhibitor since it binds at the catalytic site of Leptopsiral collagenase. Molecular dynamic simulation studies validated the stability of interaction between the active site of Leptospiral collagenase and Protohypericin. The docking and molecular simulation studies corroborated the potential of the ligand to curb leptospiral infection.

scholarly journals Transmembrane topology of the AbsA1 sensor kinase of Streptomyces coelicolor

Microbiology ◽  
2009 ◽  
Vol 155 (6) ◽  
pp. 1812-1818 ◽  
Author(s):  
Nancy L. McKenzie ◽  
Justin R. Nodwell
Keyword(s):  
Response Regulator ◽  
Streptomyces Coelicolor ◽  
Antibiotic Biosynthesis ◽  
Sensor Kinase ◽  
Response Mechanism ◽  
Transmembrane Topology ◽  
C Terminus ◽  
N Terminus ◽  
Sensor Kinases ◽  
Insight Into

The sensor kinase AbsA1 (SCO3225) phosphorylates the response regulator AbsA2 (SCO3226) and dephosphorylates AbsA2∼P. The phosphorylated response regulator represses antibiotic biosynthesis operons in Streptomyces coelicolor. AbsA1 was predicted to have an atypical transmembrane topology, and the location of its signal-sensing domain is not readily obvious. To better understand this protein and to gain insight into its signal response mechanism, we determined its transmembrane topology using fusions of absA1 to egfp, which is believed to be the first application of this approach to transmembrane topology in the actinomycetes. Our results are in agreement with the in silico topological predictions and demonstrate that AbsA1 has five transmembrane domains, four near the N terminus and one near the C terminus. Unlike most sensor kinases, the largest extracellular portion of AbsA1 is at the C terminus.

scholarly journals Sec17/Sec18 can support membrane fusion without help from completion of SNARE zippering

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Hongki Song ◽  
Thomas L Torng ◽  
Amy S Orr ◽  
Axel T Brunger ◽  
William T Wickner
Keyword(s):  
Amino Acids ◽  
Membrane Fusion ◽  
Central Region ◽  
Coiled Coils ◽  
C Terminus ◽  
N Terminus ◽  
Oligomeric Assembly ◽  
Polar Residues

Membrane fusion requires R-, Qa-, Qb-, and Qc-family SNAREs that zipper into RQaQbQc coiled coils, driven by the sequestration of apolar amino acids. Zippering has been thought to provide all the force driving fusion. Sec17/aSNAP can form an oligomeric assembly with SNAREs with the Sec17 C-terminus bound to Sec18/NSF, the central region bound to SNAREs, and a crucial apolar loop near the N-terminus poised to insert into membranes. We now report that Sec17 and Sec18 will drive robust fusion without requiring zippering completion. Zippering-driven fusion is blocked by deleting the C-terminal quarter of any Q-SNARE domain or by replacing the apolar amino acids of the Qa-SNARE which face the center of the 4-SNARE coiled coils with polar residues. These blocks, singly or combined, are bypassed by Sec17 and Sec18, and SNARE-dependent fusion is restored without help from completing zippering.

scholarly journals BVES is a novel interactor of ANO5 and regulates myoblast differentiation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haiwen Li ◽  
Li Xu ◽  
Yandi Gao ◽  
Yuanbojiao Zuo ◽  
Zuocheng Yang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Interacting Proteins ◽  
Cellular Functions ◽  
C2c12 Myoblasts ◽  
Interacting Protein ◽  
C Terminus ◽  
N Terminus ◽  
Labeling Approach

Abstract Background Anoctamin 5 (ANO5) is a membrane protein belonging to the TMEM16/Anoctamin family and its deficiency leads to the development of limb girdle muscular dystrophy R12 (LGMDR12). However, little has been known about the interactome of ANO5 and its cellular functions. Results In this study, we exploited a proximal labeling approach to identify the interacting proteins of ANO5 in C2C12 myoblasts stably expressing ANO5 tagged with BioID2. Mass spectrometry identified 41 unique proteins including BVES and POPDC3 specifically from ANO5-BioID2 samples, but not from BioID2 fused with ANO6 or MG53. The interaction between ANO5 and BVES was further confirmed by co-immunoprecipitation (Co-IP), and the N-terminus of ANO5 mediated the interaction with the C-terminus of BVES. ANO5 and BVES were co-localized in muscle cells and enriched at the endoplasmic reticulum (ER) membrane. Genome editing-mediated ANO5 or BVES disruption significantly suppressed C2C12 myoblast differentiation with little impact on proliferation. Conclusions Taken together, these data suggest that BVES is a novel interacting protein of ANO5, involved in regulation of muscle differentiation.

Role of the N-terminus in human 4-hydroxyphenylpyruvate dioxygenase activity

2019 ◽  
Vol 167 (3) ◽  
pp. 315-322
Author(s):  
An-Ning Feng ◽  
Chih-Wei Huang ◽  
Chi-Huei Lin ◽  
Yung-Lung Chang ◽  
Meng-Yuan Ni ◽  
...  
Keyword(s):  
Active Site ◽  
Catalytic Efficiency ◽  
Dynamics Simulation ◽  
Wild Type ◽  
Catalytic Function ◽  
C Terminus ◽  
N Terminus ◽  
Key Enzyme ◽  
The Stability

Abstract 4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a key enzyme in tyrosine catabolism, catalysing the oxidation of 4-hydroxyphenylpyruvate to homogentisate. Genetic deficiency of this enzyme causes type III tyrosinaemia. The enzyme comprises two barrel-shaped domains formed by the N- and C-termini, with the active site located in the C-terminus. This study investigated the role of the N-terminus, located at the domain interface, in HPPD activity. We observed that the kcat/Km decreased ∼8-fold compared with wild type upon removal of the 12 N-terminal residues (ΔR13). Interestingly, the wild-type level of activity was retained in a mutant missing the 17 N-terminal residues, with a kcat/Km 11-fold higher than that of the ΔR13 mutant; however, the structural stability of this mutant was lower than that of wild type. A 2-fold decrease in catalytic efficiency was observed for the K10A and E12A mutants, indicating synergism between these residues in the enzyme catalytic function. A molecular dynamics simulation showed large RMS fluctuations in ΔR13 suggesting that conformational flexibility at the domain interface leads to lower activity in this mutant. These results demonstrate that the N-terminus maintains the stability of the domain interface to allow for catalysis at the active site of HPPD.

scholarly journals Degradation of ornithine decarboxylase: exposure of the C-terminal target by a polyamine-inducible inhibitory protein.

1993 ◽  
Vol 13 (4) ◽  
pp. 2377-2383 ◽  
Author(s):  
X Li ◽  
P Coffino
Keyword(s):  
Conformational Change ◽  
Ornithine Decarboxylase ◽  
Binding Protein ◽  
Active Form ◽  
Feedback Regulation ◽  
Degradation Process ◽  
Protein Inhibitor ◽  
Inhibitory Protein ◽  
C Terminus ◽  
N Terminus

Polyamine-mediated degradation of vertebrate ornithine decarboxylase (ODC) is associated with the production of antizyme, a reversible tightly binding protein inhibitor of ODC activity. The interaction of antizyme with a binding element near the N terminus of ODC is essential but not sufficient for regulation of the enzyme by polyamines (X. Li and P. Coffino, Mol. Cell. Biol. 12:3556-2562, 1992). We now show that a second element present at the C terminus is required for the degradation process. Antizyme caused a conformational change in ODC, which made the C terminus of ODC more accessible. Blocking the C terminus with antibody prevented degradation. Tethering the C terminus by creating a circularly permuted, enzymatically active form of ODC prevented antizyme-mediated degradation. These data elucidate a form of feedback regulation whereby excess polyamines induce destruction of ODC, the enzyme that initiates their biosynthesis.

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