Welcome to the Recombinant Antibody Network

@article{pmid40060520,

title = {β-Amyloid Induces Microglial Expression of GPC4 and APOE Leading to Increased Neuronal Tau Pathology and Toxicity},

author = {Brandon B Holmes and Thaddeus K Weigel and Jesseca M Chung and Sarah K Kaufman and Brandon I Apresa and James R Byrnes and Kaan S Kumru and Jaime Vaquer-Alicea and Ankit Gupta and Indigo V L Rose and Yun Zhang and Alissa L Nana and Dina Alter and Lea T Grinberg and Salvatore Spina and Kevin K Leung and Carlo Condello and Martin Kampmann and William W Seeley and Jaeda C Coutinho-Budd and James A Wells},

doi = {10.1101/2025.02.20.637701},

issn = {2692-8205},

year  = {2025},

date = {2025-02-01},

urldate = {2025-02-01},

journal = {bioRxiv},

abstract = {To elucidate the impact of Aβ pathology on microglia in Alzheimer's disease pathogenesis, we profiled the microglia surfaceome following treatment with Aβ fibrils. Our findings reveal that Aβ-associated human microglia upregulate Glypican 4 (GPC4), a GPI-anchored heparan sulfate proteoglycan (HSPG). In a  amyloidosis model, glial GPC4 expression exacerbates motor deficits and reduces lifespan, indicating that glial GPC4 contributes to a toxic cellular program during neurodegeneration. In cell culture, GPC4 enhances microglia phagocytosis of tau aggregates, and shed GPC4 can act  to facilitate tau aggregate uptake and seeding in neurons. Additionally, our data demonstrate that GPC4-mediated effects are amplified in the presence of APOE. These studies offer a mechanistic framework linking Aβ and tau pathology through microglial HSPGs and APOE.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39982408,

title = {De Novo Design of Proteins That Bind Naphthalenediimides, Powerful Photooxidants with Tunable Photophysical Properties},

author = {Samuel I Mann and Zhi Lin and Sophia K Tan and Jiaqi Zhu and Zachary X W Widel and Ian Bakanas and Jarrett P Mansergh and Rui Liu and Mark J S Kelly and Yibing Wu and James A Wells and Michael J Therien and William F DeGrado},

doi = {10.1021/jacs.4c18151},

issn = {1520-5126},

year  = {2025},

date = {2025-02-01},

urldate = {2025-02-01},

journal = {J Am Chem Soc},

abstract = { protein design provides a framework to test our understanding of protein function and build proteins with cofactors and functions not found in nature. Here, we report the design of proteins designed to bind powerful photooxidants and the evaluation of the use of these proteins to generate diffusible small-molecule reactive species. Because excited-state dynamics are influenced by the dynamics and hydration of a photooxidant's environment, it was important to not only design a binding site but also to evaluate its dynamic properties. Thus, we used computational design in conjunction with molecular dynamics (MD) simulations to design a protein, designated NBP (DI inding rotein), that held a naphthalenediimide (NDI), a powerful photooxidant, in a programmable molecular environment. Solution NMR confirmed the structure of the complex. We evaluated two NDI cofactors in this  protein using ultrafast pump-probe spectroscopy to evaluate light-triggered intra- and intermolecular electron transfer function. Moreover, we demonstrated the utility of this platform to activate multiple molecular probes for protein labeling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38594044,

title = {Structural Survey of Antigen Recognition by Synthetic Human Antibodies},

author = {Maryna Gorelik and Shane Miersch and Sachdev S Sidhu},

doi = {10.1101/pdb.over107759},

issn = {1559-6095},

year  = {2025},

date = {2025-02-01},

urldate = {2025-02-01},

journal = {Cold Spring Harb Protoc},

volume = {2025},

number = {2},

pages = {pdb.over107759},

abstract = {Synthetic antibody libraries have been used extensively to isolate and optimize antibodies. To generate these libraries, the immunological diversity and the antibody framework(s) that supports it outside of the binding regions are carefully designed/chosen to ensure favorable functional and biophysical properties. In particular, minimalist, single-framework synthetic libraries pioneered by our group have yielded a vast trove of antibodies to a broad array of antigens. Here, we review their systematic and iterative development to provide insights into the design principles that make them a powerful tool for drug discovery. In addition, the ongoing accumulation of crystal structures of antigen-binding fragment (Fab)-antigen complexes generated with synthetic antibodies enables a deepening understanding of the structural determinants of antigen recognition and usage of immunoglobulin sequence diversity, which can assist in developing new strategies for antibody and library optimization. Toward this, we also survey here the structural landscape of a comprehensive and unbiased set of 50 distinct complexes derived from these libraries and compare it to a similar set of natural antibodies with the goal of better understanding how each achieves molecular recognition and whether opportunities exist for iterative improvement of synthetic libraries. From this survey, we conclude that despite the minimalist strategies used for design of these synthetic antibody libraries, the overall structural interaction landscapes are highly similar to natural repertoires. We also found, however, some key differences that can help guide the iterative design of new synthetic libraries via the introduction of positionally tailored diversity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}