BiP (immunoglobulin heavy-chain binding protein) is the endoplasmic reticulum (ER) orthologue of the Hsp70 family of molecular chaperones and is intricately involved in most functions of this organelle through its interactions with a variety of substrates and regulatory proteins. Like all Hsp70 family members, the ability of BiP to bind and release unfolded proteins is tightly regulated by a cycle of ATP binding, hydrolysis, and nucleotide exchange. As a characteristic of the Hsp70 family, multiple DnaJ-like co-factors can target substrates to BiP and stimulate its ATPase activity to stabilize the binding of BiP to substrates. However, only in the past decade have nucleotide exchange factors for BiP been identified, which has shed light not only on the mechanism of BiP-assisted folding in the ER but also on Hsp70 family members that reside throughout the cell. We will review the current understanding of the ATPase cycle of BiP in the unique environment of the ER and how it is regulated by the nucleotide exchange factors, Grp170 (glucose-regulated protein of 170kDa) and Sil1, both of which perform unanticipated roles in various biological functions and disease states.
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http://dx.doi.org/10.1016/j.jmb.2015.02.011 | DOI Listing |
mBio
January 2025
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA.
Unlabelled: Pathogenic strains cause cholera using different mechanisms. O1 and O139 serogroup strains use the toxin-co-regulated pilus (TCP) and cholera toxin (CT) for intestinal colonization and to promote secretory diarrhea, while non-O1/non-O139 serogroup strains are typically non-toxigenic and use alternate virulence factors to cause a clinically similar disease. An O39 serogroup, TCP/CT-negative strain, named AM-19226, uses a type III secretion system (T3SS) to translocate more than 10 effector proteins into the host cell cytosol.
View Article and Find Full Text PDFIndian J Occup Environ Med
December 2024
Viral Research and Diagnostic Laboratory (VRDL), Government Medical College, Patiala, Punjab, India.
Pesticides induce oxidative DNA damage and genotoxic effects such as DNA single-strand breaks (SSBs), double-strand breaks (DSBs), DNA adducts, chromosomal aberrations, and enhanced sister chromatid exchanges. Such DNA damage can be repaired by DNA repair mechanisms. In humans, single nucleotide polymorphisms (SNPs) are present in DNA repair genes involved in base excision repair (BER) (, and nucleotide excision repair (NER) (, , , and ), and double-strand break repair (DSBR) ( and ).
View Article and Find Full Text PDFNat Commun
January 2025
Department of Molecular Biosciences, University of South Florida, 4202 E Fowler Ave, Tampa, FL, 33620, USA.
Unraveling the signaling roles of intermediate complexes is pivotal for G protein-coupled receptor (GPCR) drug development. Despite hundreds of GPCR-Gαβγ structures, these snapshots primarily capture the fully activated complex. Consequently, the functions of intermediate GPCR-G protein complexes remain elusive.
View Article and Find Full Text PDFSci Signal
January 2025
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
The small GTPase R-RAS2 regulates homeostatic proliferation and survival of T and B lymphocytes and, when present in high amounts, drives the development of B cell chronic lymphocytic leukemia. In normal and leukemic lymphocytes, R-RAS2 constitutively binds to antigen receptors through their immunoreceptor tyrosine-based activation motifs (ITAMs) and promotes tonic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Here, we examined the molecular mechanisms underlying this direct interaction and its consequences for R-RAS2 activity.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Departments of Physics, Cell Biology and Biochemistry, Emory University, Atlanta, GA 30322.
Cellular actin networks exhibit distinct assembly and disassembly dynamics, primarily driven by multicomponent reactions occurring at the two ends of actin filaments. While barbed ends are recognized as the hotspot for polymerization, depolymerization is predominantly associated with pointed ends. Consequently, mechanisms promoting barbed-end depolymerization have received relatively little attention.
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