Aggregation properties of the small nuclear ribonucleoprotein U1-70K in Alzheimer disease.
AuthorsDiner I, Hales CM, Bishof I, Rabenold L, Duong DM, Yi H, Laur O, Gearing M, Troncoso J, Thambisetty M, Lah JJ, Levey AI, Seyfried NT
Journal
PubMed ID25355317
Recent evidence indicates that U1-70K and other U1 small nuclear ribonucleoproteins are Sarkosyl-insoluble and associate with Tau neurofibrillary tangles selectively in Alzheimer disease (AD). Currently, the mechanisms underlying the conversion of soluble nuclear U1 small nuclear ribonucleoproteins into insoluble cytoplasmic aggregates remain elusive. Based on the biochemical and subcellular distribution ... More
NELL2-Robo3 complex structure reveals mechanisms of receptor activation for axon guidance.
AuthorsPak JS, DeLoughery ZJ, Wang J, Acharya N, Park Y, Jaworski A, Özkan E
JournalNat Commun
PubMed ID32198364
'Axon pathfinding is critical for nervous system development, and it is orchestrated by molecular cues that activate receptors on the axonal growth cone. Robo family receptors bind Slit guidance cues to mediate axon repulsion. In mammals, the divergent family member Robo3 does not bind Slits, but instead signals axon repulsion ... More
Combining Structure-Function and Single-Molecule Studies on Cytoplasmic Dynein.
AuthorsRao L, Hülsemann M, Gennerich A
JournalMethods Mol Biol
PubMed ID28940064
'Cytoplasmic dynein is the largest and most intricate cytoskeletal motor protein. It is responsible for a vast array of biological functions, ranging from the transport of organelles and mRNAs to the movement of nuclei during neuronal migration and the formation and positioning of the mitotic spindle during cell division. Despite ... More
Differences in Glycoprotein Complex Receptor Binding Site Accessibility Prompt Poor Cross-Reactivity of Neutralizing Antibodies between Closely Related Arenaviruses.
AuthorsBrouillette RB, Phillips EK, Ayithan N, Maury W
JournalJ Virol
PubMed ID28100617
The glycoprotein complex (GPC) of arenaviruses, composed of stable signal peptide, GP1, and GP2, is the only antigen correlated with antibody-mediated neutralization. However, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. Two closely related clade B viruses, Machupo virus (MACV) and Junín virus ... More
The anti-SLAMF7 antibody elotuzumab mediates NK cell activation through both CD16-dependent and -independent mechanisms.
AuthorsPazina T, James AM, MacFarlane AW, Bezman NA, Henning KA, Bee C, Graziano RF, Robbins MD, Cohen AD, Campbell KS
JournalOncoimmunology
PubMed ID28932638
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab ... More
Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex.
AuthorsCardote TAF, Gadd MS, Ciulli A
JournalStructure
PubMed ID28591624
Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system to catalyze the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins. CRLs are large dynamic complexes and attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. The atomic details ... More
The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization.
AuthorsLei L, Yang YR, Tran K, Wang Y, Chiang CI, Ozorowski G, Xiao Y, Ward AB, Wyatt RT, Li Y
JournalCell Rep
PubMed ID30970260
Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate ... More
Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity.
AuthorsSeo JA, Kang MC, Yang WM, Hwang WM, Kim SS, Hong SH, Heo JI, Vijyakumar A, Pereira de Moura L, Uner A, Huang H, Lee SH, Lima IS, Park KS, Kim MS, Dagon Y, Willnow TE, Aroda V, Ciaraldi TP, Henry RR, Kim YB
JournalNat Commun
PubMed ID32332780
Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related ... More
Avidin-biotin technology to synthesize multi-arm nano-construct for drug delivery.
AuthorsZhang C, He T, Vedadghavami A, Bajpayee AG
JournalMethodsX
PubMed ID32405463
Here we describe methods for synthesizing a cationic, multi-arm Avidin (mAv) nano-construct that has a wide range of applications in drug delivery and imaging of negatively charged tissues. We use Avidin-biotin technology that gives the flexibility for conjugating biotinylated Dexamethasone to mAv by simple mixing at room temperature. We also ... More
Target-responsive vasoactive probes for ultrasensitive molecular imaging.
AuthorsOhlendorf R, Wisniowska A, Desai M, Barandov A, Slusarczyk AL, Li N, Jasanoff A
JournalNat Commun
PubMed ID32404879
The ability to monitor molecules volumetrically throughout the body could provide valuable biomarkers for studies of healthy function and disease, but noninvasive detection of molecular targets in living subjects often suffers from poor sensitivity or selectivity. Here we describe a family of potent imaging probes that can be activated by ... More
Erythrocytes as Carriers: From Drug Delivery to Biosensors.
AuthorsKoleva L, Bovt E, Ataullakhanov F, Sinauridze E
JournalPharmaceutics
PubMed ID32197542
Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Such erythrocytes can act as carriers that prolong the drug's action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma ... More
Disruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis.
AuthorsWang JJ, Liu F, Yang F, Wang YZ, Qi X, Li Y, Hu Q, Zhu MX, Xu TL
JournalNat Commun
PubMed ID31980622
We reported previously that acid-sensing ion channel 1a (ASIC1a) mediates acidic neuronal necroptosis via recruiting receptor-interacting protein kinase 1 (RIPK1) to its C terminus (CT), independent of its ion-conducting function. Here we show that the N-terminus (NT) of ASIC1a interacts with its CT to form an auto-inhibition that prevents RIPK1 ... More
Application of an antibody chip for screening differentially expressed proteins during peach ripening and identification of a metabolon in the SAM cycle to generate a peach ethylene biosynthesis model.
AuthorsZeng W, Niu L, Wang Z, Wang X, Wang Y, Pan L, Lu Z, Cui G, Weng W, Wang M, Meng X, Wang Z
JournalHortic Res
PubMed ID32194967
Peach (
An amber obligate active site-directed ligand evolution technique for phage display.
AuthorsTharp JM, Hampton JT, Reed CA, Ehnbom A, Chen PC, Morse JS, Kurra Y, Pérez LM, Xu S, Liu WR
JournalNat Commun
PubMed ID32170178
Although noncanonical amino acids (ncAAs) were first incorporated into phage libraries through amber suppression nearly two decades ago, their application for use in drug discovery has been limited due to inherent library bias towards sense-containing phages. Here, we report a technique based on superinfection immunity of phages to enrich amber-containing ... More