scholarly journals Cryo-EM structures of the air-oxidized and dithionite-reduced photosynthetic alternative complex III from Roseiflexus castenholzii

2020 ◽  
Vol 6 (31) ◽  
pp. eaba2739 ◽  
Author(s):  
Yang Shi ◽  
Yueyong Xin ◽  
Chao Wang ◽  
Robert E. Blankenship ◽  
Fei Sun ◽  
...  
Keyword(s):  
Proton Translocation ◽  
Photosynthetic Electron Transport ◽  
Photosynthetic Bacterium ◽  
Binding Pocket ◽  
Bacterial Photosynthesis ◽  
Complex Iii ◽  
Structural Basis ◽  
Coupling Mechanism ◽  
Electron Transport Chains ◽  
Alternative Complex Iii

Alternative complex III (ACIII) is a multisubunit quinol:electron acceptor oxidoreductase that couples quinol oxidation with transmembrane proton translocation in both the respiratory and photosynthetic electron transport chains of bacteria. The coupling mechanism, however, is poorly understood. Here, we report the cryo-EM structures of air-oxidized and dithionite-reduced ACIII from the photosynthetic bacterium Roseiflexus castenholzii at 3.3- and 3.5-Å resolution, respectively. We identified a menaquinol binding pocket and an electron transfer wire comprising six hemes and four iron-sulfur clusters that is capable of transferring electrons to periplasmic acceptors. We detected a proton translocation passage in which three strictly conserved, mid-passage residues are likely essential for coupling the redox-driven proton translocation across the membrane. These results allow us to propose a previously unrecognized coupling mechanism that links the respiratory and photosynthetic functions of ACIII. This study provides a structural basis for further investigation of the energy transformation mechanisms in bacterial photosynthesis and respiration.

scholarly journals Structural basis for energy transduction by respiratory alternative complex III

2018 ◽  
Vol 1859 ◽  
pp. e18-e19
Author(s):  
Manuela M. Pereira ◽  
Joana S. Sousa ◽  
Filipa Calisto ◽  
Deryck J. Mills ◽  
Julian D. Langer ◽  
...  
Keyword(s):  
Energy Transduction ◽  
Complex Iii ◽  
Structural Basis ◽  
Alternative Complex Iii

scholarly journals Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Kalyan Das ◽  
Sergio E. Martinez ◽  
Eddy Arnold
Keyword(s):  
Reverse Transcriptase ◽  
Binding Pocket ◽  
Complex Iii ◽  
Structural Basis ◽  
Single Mutation ◽  
Wild Type ◽  
Chain Flexibility ◽  
Multiple Drugs ◽  
Dntp Binding ◽  
Hiv 1

ABSTRACT HIV-1 reverse transcriptase (RT) is targeted by multiple drugs. RT mutations that confer resistance to nucleoside RT inhibitors (NRTIs) emerge during clinical use. Q151M and four associated mutations, A62V, V75I, F77L, and F116Y, were detected in patients failing therapies with dideoxynucleosides (didanosine [ddI], zalcitabine [ddC]) and/or zidovudine (AZT). The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs. To understand the structural basis for Q151M and Q151Mc resistance, we systematically determined the crystal structures of the wild-type RT/double-stranded DNA (dsDNA)/dATP (complex I), wild-type RT/dsDNA/ddATP (complex II), Q151M RT/dsDNA/dATP (complex III), Q151Mc RT/dsDNA/dATP (complex IV), and Q151Mc RT/dsDNA/ddATP (complex V) ternary complexes. The structures revealed that the deoxyribose rings of dATP and ddATP have 3′-endo and 3′-exo conformations, respectively. The single mutation Q151M introduces conformational perturbation at the deoxynucleoside triphosphate (dNTP)-binding pocket, and the mutated pocket may exist in multiple conformations. The compensatory set of mutations in Q151Mc, particularly F116Y, restricts the side chain flexibility of M151 and helps restore the DNA polymerization efficiency of the enzyme. The altered dNTP-binding pocket in Q151Mc RT has the Q151-R72 hydrogen bond removed and has a switched conformation for the key conserved residue R72 compared to that in wild-type RT. On the basis of a modeled structure of hepatitis B virus (HBV) polymerase, the residues R72, Y116, M151, and M184 in Q151Mc HIV-1 RT are conserved in wild-type HBV polymerase as residues R41, Y89, M171, and M204, respectively; functionally, both Q151Mc HIV-1 and wild-type HBV are resistant to dideoxynucleoside analogs.

scholarly journals Structural Basis and Mechanism of Proton Translocation in Complex I and Complex III

2011 ◽  
Vol 100 (3) ◽  
pp. 343a
Author(s):  
Carola Hunte
Keyword(s):  
Complex I ◽  
Proton Translocation ◽  
Complex Iii ◽  
Structural Basis

scholarly journals Structural basis for energy transduction by respiratory alternative complex III

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Joana S. Sousa ◽  
Filipa Calisto ◽  
Julian D. Langer ◽  
Deryck J. Mills ◽  
Patrícia N. Refojo ◽  
...  
Keyword(s):  
Energy Transduction ◽  
Complex Iii ◽  
Structural Basis ◽  
Alternative Complex Iii

Plastoquinones in photosynthesis

1978 ◽  
Vol 284 (1002) ◽  
pp. 591-599 ◽  
Keyword(s):  
Electron Transport ◽  
Photosystem Ii ◽  
Energy Conservation ◽  
Thylakoid Membrane ◽  
Electron Flow ◽  
Proton Translocation ◽  
Photosynthetic Electron Transport ◽  
Atp Formation ◽  
Electron Transport Chains

Several plastoquinones with different or modified side chains have been characterized in plant material: they are localized in the inner thylakoid membrane of the chloroplast. So far only plastoquinone-45 (PQ-45) has been identified as an obligatory functional component of the photosynthetic electron transport chain in chloroplasts between photosystem II and photosystem I. A special form (semiquinone) of PQ-45 acts as primary acceptor Q of photosystem II, a large pool of PQ-45 as electron buffer, interconnecting several electron transport chains. The rôle of PQ, in energy conservation (ATP formation) is of particular current interest. Owing to vectorial electron flow across the thylakoid membrane, plastoquinone is thought to be reduced on the outside and plastohydroquinone to be oxidized on the inside of the membrane. This results in a proton translocation across the membrane and a build-up of a proton motive force which drives ATP formation. Old and new plastoquinone antagonists are described and the relevance of inhibitor studies on the rôle of plastoquinone in electron flow and photophosphorylation is discussed. Open questions and current problems of the mechanism of plastoquinone/plastoquinol transport across the membrane - and of proton translocation connected to it - relevant for the mechanism of energy conservation in photosynthesis, are pointed out.

scholarly journals Structural basis of mechano-chemical coupling by the mitotic kinesin KIF14

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matthieu P.M.H. Benoit ◽  
Ana B. Asenjo ◽  
Mohammadjavad Paydar ◽  
Sabin Dhakal ◽  
Benjamin H. Kwok ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Atp Hydrolysis ◽  
Nucleotide Binding ◽  
Binding Pocket ◽  
Bound State ◽  
Structural Basis ◽  
Coupling Mechanism ◽  
Developmental Defects ◽  
Microtubule Binding

AbstractKIF14 is a mitotic kinesin whose malfunction is associated with cerebral and renal developmental defects and several cancers. Like other kinesins, KIF14 couples ATP hydrolysis and microtubule binding to the generation of mechanical work, but the coupling mechanism between these processes is still not fully clear. Here we report 20 high-resolution (2.7–3.9 Å) cryo-electron microscopy KIF14-microtubule structures with complementary functional assays. Analysis procedures were implemented to separate coexisting conformations of microtubule-bound monomeric and dimeric KIF14 constructs. The data provide a comprehensive view of the microtubule and nucleotide induced KIF14 conformational changes. It shows that: 1) microtubule binding, the nucleotide species, and the neck-linker domain govern the transition between three major conformations of the motor domain; 2) an undocked neck-linker prevents the nucleotide-binding pocket to fully close and dampens ATP hydrolysis; 3) 13 neck-linker residues are required to assume a stable docked conformation; 4) the neck-linker position controls the hydrolysis rather than the nucleotide binding step; 5) the two motor domains of KIF14 dimers adopt distinct conformations when bound to the microtubule; and 6) the formation of the two-heads-bound-state introduces structural changes in both motor domains of KIF14 dimers. These observations provide the structural basis for a coordinated chemo-mechanical kinesin translocation model.

Structural Insights into Azole-based Inhibitors of Heme Oxygenase-1: Development of Selective Compounds for Therapeutic Applications

2019 ◽  
Vol 25 (42) ◽  
pp. 5803-5821 ◽  
Author(s):  
Mona N. Rahman ◽  
Dragic Vukomanovic ◽  
Jason Z. Vlahakis ◽  
Walter A. Szarek ◽  
Kanji Nakatsu ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Competitive Inhibition ◽  
Cytochromes P450 ◽  
Structural Similarity ◽  
Binding Pocket ◽  
Initial Study ◽  
Structural Basis ◽  
Heme Oxygenase 1 ◽  
Design Strategies ◽  
Inhibitor Binding

The development of isozyme-selective heme oxygenase (HO) inhibitors promises powerful pharmacological tools to elucidate the regulatory characteristics of the HO system. It is already known that HO has cytoprotective properties with a role in several disease states; thus, it is an enticing therapeutic target. Historically, the metalloporphyrins have been used as competitive HO inhibitors based on their structural similarity to the substrate, heme. However, heme’s important role in several other proteins (e.g. cytochromes P450, nitric oxide synthase), results in non-selectivity being an unfortunate side effect. Reports that azalanstat and other non-porphyrin molecules inhibited HO led to a multi-faceted effort over a decade ago to develop novel compounds as potent, selective inhibitors of HO. The result was the creation of the first generation of non-porphyrin based, non-competitive inhibitors with selectivity for HO, including a subset with isozyme selectivity for HO-1. Using X-ray crystallography, the structures of several complexes of HO-1 with novel inhibitors have been elucidated and provided insightful information regarding the salient features required for inhibitor binding. This included the structural basis for non-competitive inhibition, flexibility and adaptability of the inhibitor binding pocket, and multiple, potential interaction subsites, all of which can be exploited in future drug-design strategies. Notably, HO-1 inhibitors are of particular interest for the treatment of hyperbilirubinemia and certain types of cancer. Key features based on this initial study have already been used by others to discover additional potential HO-1 inhibitors. Moreover, studies have begun to use selected compounds and determine their effects in some disease models.

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