Welcome to the Recombinant Antibody Network

@article{pmid41807832,

title = {Structures of ALG3/9/12 reveal the assembly logic of the N-glycan oligomannose core},

author = {J Andrew N Alexander and Shu-Yu Chen and Somnath Mukherjee and Mario de Capitani and Rossitza N Irobalieva and Lorenzo Rossi and Parth Agrawal and Julia Kowal and Matheus A Meirelles and Markus Aebi and Jean-Louis Reymond and Anthony A Kossiakoff and Sereina Riniker and Kaspar P Locher},

doi = {10.1038/s41589-026-02164-7},

issn = {1552-4469},

year  = {2026},

date = {2026-03-01},

urldate = {2026-03-01},

journal = {Nat Chem Biol},

abstract = {Asparagine-linked glycans are essential for the maturation and function of most eukaryotic secretory proteins. The biosynthesis and transfer of dolichylpyrophosphate-anchored GlcNAcManGlc glycan is a highly conserved process occurring in the endoplasmic reticulum (ER) membrane and involving over a dozen membrane proteins whose dysfunction is linked to congenital disorders of glycosylation (CDGs). Three membrane-integral mannosyltransferases, ALG3, ALG9 and ALG12, mediate four consecutive mannosylation reactions that convert GlcNAcMan to GlcNAcMan. Here, using chemoenzymatically synthesized lipid-linked glycan donor and acceptor analogs, we recapitulated this biosynthetic pathway in vitro. High-resolution cryo-electron microscopy structures of pseudo-Michaelis complexes of each step revealed how the branched glycan is accurately synthesized and unwanted side products are averted. Molecular dynamics simulations and mutagenesis studies uncovered a subtle but precise mechanism selecting the dolichylphosphomannose donor substrate over dolichylphosphoglucose, which is also present in the ER membrane. Our results also provide mechanistic explanations for enzyme dysfunction in CDGs and offer opportunities for N-glycan engineering.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41756920,

title = {Targeted shedding of extracellular membrane proteins by induced protease recruitment},

author = {Zi Yao and Fangzhu Zhao and Kun Miao and Trenton M Peters-Clarke and Yun Zhang and Snehal D Ganjave and Angel L Vázquez-Maldonado and Yan Wu and Kaan Kumru and Hammam Jumaa and Kevin K Leung and James A Wells},

doi = {10.64898/2026.02.17.706468},

issn = {2692-8205},

year  = {2026},

date = {2026-02-01},

urldate = {2026-02-01},

journal = {bioRxiv},

abstract = {Extracellular targeted protein degradation has emerged as a promising therapeutic modality to eliminate proteins of interest (POIs) at the cell surface, by using bifunctional molecules to recruit natural recycling receptors or membrane-bound E3 ligases that redirect POIs to the lysosome. Another natural mechanism involves extracellular proteases that cleave and shed extracellular domains. Here, we exploit this endogenous mechanism by engineering bispecific antibody  , that recruit a classic sheddase ADAM10 to POIs, inducing selective ectodomain shedding. We first targeted the immune checkpoint receptor LAG-3 and observed robust depletion of surface LAG-3 accompanied by accumulation of soluble LAG-3 fragments in both engineered cell lines and primary human T cells. Using biochemical and imaging assays, we confirmed that this antibody-induced shedding is restricted to extracellular protease activity and occurs independently of lysosomal trafficking. Notably, induced shedding of LAG-3 on activated primary T cells partially alleviated inhibitory signaling and reinvigorated IFN  secretion. We extended the scope of induced shedding by developing  that recognize synthetic epitope-tags that enabling rapid assessment of substrate compatibility across diverse targets. Using this platform, we identified multiple immune modulatory cell-surface receptors, including IL6Rα, CD62L and MIC-A that can be targeted for shedding. In summary, this work establishes a new paradigm for targeted extracellular proteolysis and expands the toolkit for studying extracellular proteolysis with potential therapeutic benefit.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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}

}