Welcome to the Recombinant Antibody Network

@article{pmid41701836,

title = {Conformational ensembles of the magnesium channel CorA reveal structural basis for channel gating},

author = {Satchal K Erramilli and Kamil Nosol and Krzysztof Pietrzak-Lichwa and Nicolaus Schmandt and Tian Li and Piotr Tokarz and Jingkai Hou and Minglei Zhao and Eduardo Perozo and Anthony A Kossiakoff},

doi = {10.1073/pnas.2512532123},

issn = {1091-6490},

year  = {2026},

date = {2026-02-01},

urldate = {2026-02-01},

journal = {Proc Natl Acad Sci U S A},

volume = {123},

number = {8},

pages = {e2512532123},

abstract = {In prokaryotes, CorA is the primary influx pathway for magnesium, a critical divalent cation in cellular physiology and biochemistry. Mechanistic studies show that homopentameric CorA is regulated through an intracellular [Mg]-dependent negative feedback loop, involving the asymmetric participation of individual subunits. To understand the connection between asymmetry and activation, we used single-particle cryo-EM to solve sixteen structures of nanodisc-reconstituted CorA. We utilized conformation-specific synthetic antibodies to stabilize subtle but significant conformational differences in the cryo-EM structures. Our results demonstrate that CorA exists as a set of conformational ensembles, where population size inversely correlates with intracellular Mg concentration. These ensembles include channels with a variety of pore conformations, both constricted and dilated, suggesting a spectrum of active CorA functional states. The ensembles connect asymmetric structural transitions in the cytoplasmic domain with conformational changes in the permeation pathway via an electrostatic network, ultimately controlling channel-gating events. We believe that these results establish a framework for understanding magnesium homeostasis in prokaryotic systems.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41556618,

title = {Tetravalent antibodies are more potent and efficacious erythropoiesis-stimulating agents than erythropoietin in vivo},

author = {Jarrett J Adams and Levi L Blazer and Jacky Chung and Minoo Karimi and Taylor Davidson and Bailey Blair and Carlos Waddle and Craig A Hokanson and Heather A Bruce and Alexander U Singer and Eva-Maria Tombak and Kiira Gildemann and Nele Tamberg and Kaja Kiiver and Mart Ustav and Yue Ma and Luigi Colombo and Lily Jun-Shen Huang and Stephen W Michnick and Orson W Moe and Sachdev S Sidhu},

doi = {10.1002/pro.70462},

issn = {1469-896X},

year  = {2026},

date = {2026-02-01},

urldate = {2026-02-01},

journal = {Protein Sci},

volume = {35},

number = {2},

pages = {e70462},

abstract = {Recent studies have shown that tetravalent antibodies are potent and efficacious agonists of the erythropoietin (EPO) receptor (EPOR) both in vitro and in vivo. To identify antibody-based erythropoiesis-stimulating agents (ESAs) with therapeutic potential, we evaluated various tetravalent antibody formats for EPOR agonism and key biophysical properties necessary for biologic drug development. We identified two distinct tetravalent antibody formats that strongly stimulated the growth of UT7/Epo cells, which rely on EPOR signaling for proliferation. Moreover, one of these formats exhibited ideal biophysical characteristics for drug development. This format consisted of a diabody (Db) and two antigen-binding fragment (Fab) arms fused to the N- and C-termini of an Fc domain, respectively, to form a tetravalent Db-Fc-Fab (EPRA-0322). In a mouse model expressing the human EPOR, EPRA-0322 induced erythropoiesis with greater potency, efficacy, and duration than darbepoetin, a hyperglycosylated EPO currently used in clinical practice. These findings highlight tetravalent antibodies, and the Db-Fc-Fab format in particular, as promising next-generation ESAs suitable for large-scale production and clinical use.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41254216,

title = {Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap},

author = {Zhi Lin and Wayne Ngo and Yu-Ting Chou and Harry Wu and Katherine J Susa and Young-Wook Jun and Trever G Bivona and Jennifer A Doudna and James A Wells},

doi = {10.1038/s41589-025-02076-y},

issn = {1552-4469},

year  = {2026},

date = {2026-02-01},

urldate = {2025-11-01},

journal = {Nat Chem Biol},

volume = {22},

number = {2},

pages = {192--204},

abstract = {Photoproximity labeling proteomics (PLP) methods have recently shown that cell surface receptors can form lateral interactome networks. Here, we present a paired set of PLP workflows that dynamically track neighborhood changes for oncogenic epidermal growth factor receptor (EGFR) over time, both outside and inside of cells. We achieved this by augmenting the multiscale PLP workflow we call MultiMap, where three photoprobes with different labeling ranges were photoactivated by one photocatalyst, eosin Y, anchored extracellularly and intracellularly on EGFR. We identified hundreds of neighboring proteins that changed within minutes to over 1 h after the addition of EGF. These neighborhoods reveal dynamic interactomes during early, middle and late signaling that drive phosphorylation, internalization, degradation and transcriptional regulation. This rapid 'molecular photographic' labeling approach provides snapshots of signaling neighborhoods, revealing their dynamic nature and potential for drug targeting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}