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Last update 23 Jan 2025

GRPEL1

Last update 23 Jan 2025

Basic Info

Synonyms

FLJ25609, GREPEL1, GrpE

+ [5]

Introduction

Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner (By similarity). Seems to control the nucleotide-dependent binding of mitochondrial HSP70 to substrate proteins (PubMed:11311562).

Drugs associated with GRPEL1

CN116023505

Patent Mining

Target

GRPEL1

Mechanism-

Active Org.

Lanzhou University

Originator Org.

Lanzhou University

Active Indication

Infectious Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GRPEL1

100 Translational Medicine associated with GRPEL1

0 Patents (Medical) associated with GRPEL1

677

Literatures (Medical) associated with GRPEL1

01 Jan 2025·International Journal of Food Microbiology

Disruption of the signal recognition particle pathway leading to impaired growth, sugar metabolism and acid resistance of Lactococcus lactis

Article

Author: Zhu, Xiaoce ; Guo, Tingting ; Zhang, Yifei ; Wang, Meng ; Kong, Jian ; Yue, Yanying ; Wang, Mengjie

Lactococcus lactis is a well-known workhorse for dairy products, whose important industrial traits are tightly associated with numerous cytoplasmic membrane proteins. However, roles of the signal recognition particle (SRP) pathway responsible for membrane protein targeting have not been studied in L. lactis. In this work, the putative genes ffh and ftsY encoding SRP pathway components were identified in the genome of L. lactis NZ9000. Experimental evidence showed that sequence mutation in either the ffh or ftsY was not lethal, but prolonged the lag phase of the resultant mutants Δffh and ΔftsY by 2 h and lowered their biomass to 85.7 % of the wild type under static conditions, as well as deprived the mutants of improved growth capacity under aerobic respiration conditions. Besides, the speeds of glucose consumption and lactate production were significantly decreased in the mutants. Then, the impact of the SPR components on acid resistance was detected, showing that the ffh and ftsY were transcriptionally upregulated by 3.02 ± 1.21 and 8.66 ± 1.01-fold in the wild type during acid challenge at pH 3.0, and cell survival of the Δffh and ΔftsY decreased by10- and 100-fold compared with the wild type. To explore the possible mechanism about the SRP pathway involved in the above physiological traits, proteomics analysis was performed and revealed that disruption of the Ffh or FtsY led to decrease in ribosomal proteins, but increase in DnaK, GroEL and heat shock protein GrpE, indicating that the SRP pathway was closely linked to protein synthesis and folding in L. lactis. Decrease in the fructose-bisphosphate aldolase, respiratory complexes NADH dehydrogenase, as well as glutamate decarboxylase was also detected in the Δffh and ΔftsY, which is consistent with the phenomena of impaired sugar metabolism and acid resistance. Our results demonstrated the dispensable SRP pathway could contribute to the maintenance of metabolism homeostasis and acid resistance of L. lactis.

01 Dec 2024·Current Radiopharmaceuticals

RGIE: A Gene Selection Method Related to Radiotherapy Resistance in Head and Neck Squamous Cell Carcinoma

Article

Author: Yang, Liying ; Li, Huan ; Liu, Rong ; Huang, Junhong ; Gao, Wanpeng ; Wei, Jianhua ; Yang, Zihui ; Li, Yahui ; Liu, Dunhui ; Wang, Jun ; Yang, Xinjie ; Meng, Qingzhe

Background::Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignant tumor with a high degree of malignancy, invasiveness, and metastasis rate. Radiotherapy, as an important adjuvant therapy for HNSCC, can reduce the postoperative recurrence rate and improve the survival rate. Identifying the genes related to HNSCC radiotherapy resistance (HNSCC-RR) is helpful in the search for potential therapeutic targets. However, identifying radiotherapy resistance-related genes from tens of thousands of genes is a challenging task. While interactions between genes are important for elucidating complex biological processes, the large number of genes makes the computation of gene interactions infeasible.Methods::We propose a gene selection algorithm, RGIE, which is based on ReliefF, Gene Network Inference with Ensemble of Trees (GENIE3) and Feature Elimination. ReliefF was used to select a feature subset that is discriminative for HNSCC-RR, GENIE3 constructed a gene regulatory network based on this subset to analyze the regulatory relationship among genes, and feature elimination was used to remove redundant and noisy features.Results::Nine genes (SPAG1, FIGN, NUBPL, CHMP5, TCF7L2, COQ10B, BSDC1, ZFPM1, GRPEL1) were identified and used to identify HNSCC-RR, which achieved performances of 0.9730, 0.9679, 0.9767, and 0.9885 in terms of accuracy, precision, recall, and AUC, respectively. Finally, qRT-PCR validated the differential expression of the nine signature genes in cell lines (SCC9, SCC9-RR).Conclusion::RGIE is effective in screening genes related to HNSCC-RR. This approach may help guide clinical treatment modalities for patients and develop potential treatments.

01 Nov 2024·Protein Science

Preferential binding of ADP‐bound mitochondrial HSP70 to the nucleotide exchange factor GRPEL1 over GRPEL2

Article

Author: Tyynismaa, Henna ; Stojkovič, Gorazd ; Manjunath, Pooja ; Euro, Liliya ; Konovalova, Svetlana ; Wanrooij, Sjoerd ; Koski, Kristian

AbstractHuman nucleotide exchange factors GRPEL1 and GRPEL2 play pivotal roles in the ADP–ATP exchange within the protein folding cycle of mitochondrial HSP70 (mtHSP70), a crucial chaperone facilitating protein import into the mitochondrial matrix. Studies in human cells and mice have indicated that while GRPEL1 serves as an essential co‐chaperone for mtHSP70, GRPEL2 has a role regulated by stress. However, the precise structural and biochemical mechanisms underlying the distinct functions of the GRPEL proteins have remained elusive. In our study, we present evidence revealing that ADP‐bound mtHSP70 exhibits remarkably higher affinity for GRPEL1 compared to GRPEL2, with the latter experiencing a notable decrease in affinity upon ADP binding. Additionally, Pi assay showed that GRPEL1, but not GRPEL2, enhanced the ATPase activity of mtHSP70. Utilizing Alphafold modeling, we propose that the interaction between GRPEL1 and mtHSP70 can induce the opening of the nucleotide binding cleft of the chaperone, thereby facilitating the release of ADP, whereas GRPEL2 lacks this capability. Additionally, our findings suggest that the redox‐regulated Cys87 residue in GRPEL2 does not play a role in dimerization but rather reduces its affinity for mtHSP70. Our findings on the structural and functional disparities between GRPEL1 and GRPEL2 may have implications for mitochondrial protein folding and import processes under varying cellular conditions.

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