Category Archives: Structure

Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2.






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Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2.

Structure. 2017 Aug 01;25(8):1163-1174

Authors: Zak KM, Grudnik P, Magiera K, Dömling A, Dubin G, Holak TA

Abstract
Cancer cells can avoid and suppress immune responses through activation of inhibitory immune checkpoint proteins, such as PD-1, PD-L1, and CTLA-4. Blocking the activities of these proteins with monoclonal antibodies, and thus restoring T cell function, has delivered breakthrough therapies against cancer. In this review, we describe the latest work on structural characterization of the checkpoint proteins, their interactions with cognate ligands and with therapeutic antibodies. Structures of the extracellular portions of these proteins reveal that they all have a similar modular structure, composed of small domains similar in topology to the domains found in antibodies. Structural basis for blocking the PD-1/PD-L1 interaction by small molecules is illustrated with the compound BMS-202 that binds to and induces dimerization of PD-L1.

PMID: 28768162 [PubMed – in process]

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Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1.






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Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1.

Structure. 2015 Oct 22;

Authors: Zak KM, Kitel R, Przetocka S,…

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Distinctive Properties of the Nuclear Localization Signals of Inner Nuclear Membrane Proteins Heh1 and Heh2.






Distinctive Properties of the Nuclear Localization Signals of Inner Nuclear Membrane Proteins Heh1 and Heh2.

Structure. 2015 May 19;

Authors: Lokareddy RK, Hapsari RA, van Rheenen M, Pumroy RA, Bhardwaj A, Steen A, Veenhoff LM, Cingolani G

Abstract
Targeting of ER-synthesized membrane proteins to the inner nuclear membrane (INM) has long been explained by the diffusion-retention model. However, several INM proteins contain non-classical nuclear localization signal (NLS) sequences, which, in a few instances, have been shown to promote importin α/β- and Ran-dependent translocation to the INM. Here, using structural and biochemical methods, we show that yeast INM proteins Heh2 and Src1/Heh1 contain bipartite import sequences that associate intimately with the minor NLS-binding pocket of yeast importin α and unlike classical NLSs efficiently displace the IBB domain in the absence of importin β. In vivo, the intimate interactions at the minor NLS-binding pocket make the h2NLS highly efficient at recruiting importin α at the ER and drive INM localization of endogenous Heh2. Thus, h1/h2NLSs delineate a novel class of super-potent, IBB-like membrane protein NLSs, distinct from classical NLSs found in soluble cargos and of general interest in biology.

PMID: 26051712 [PubMed – as supplied by publisher]

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Functional diversity of tandem substrate-binding domains in ABC transporters from pathogenic bacteria.






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Functional diversity of tandem substrate-binding domains in ABC transporters from pathogenic bacteria.
Structure. 2013 Oct 8;21(10):1879-88
Authors: Fulyani F, Schuurman-Wolters GK, Zagar AV, Guskov … Continue reading






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Substrate-induced conformational changes in the S-component ThiT from an energy coupling factor transporter.






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Substrate-induced conformational changes in the S-component ThiT from an energy coupling factor transporter.

Structure. 2013 May 7;21(5):861-7

Authors: …

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Spotting the mistakes, one molecule at a time.






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Spotting the mistakes, one molecule at a time.

Structure. 2012 Jul 3;20(7):1130-2

Authors: Quessada-Vial A, van Oijen AM

Abstract

In…

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Quantitative Analysis of the Interaction Strength and Dynamics of Human IgG4 Half Molecules by Native Mass Spectrometry.






Quantitative Analysis of the Interaction Strength and Dynamics of Human IgG4 Half Molecules by Native Mass Spectrometry.
Structure. 2011 Sep 7;19(9):1274-82
Authors: Rose RJ, Labrijn AF, van den Bremer ET, Loverix S, Lasters I… Continue reading






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