6SUA

Structure of the high affinity engineered lipocalin C1B12 in complex with the mouse CD98 heavy chain ectodomain

Summary for 6SUA

• Entry DOI: 10.2210/pdb6sua/pdb
• Descriptor: Neutrophil gelatinase-associated lipocalin, 4F2 cell-surface antigen heavy chain, SULFATE ION, ... (4 entities in total)
• Functional Keywords: lipocalin, lcn2, anticalin, lipocalin-based binding protein, cd98hc, 4f2hc, amino acid transport, presentation of cd98 light chain, interaction with integrin beta subunit, single-pass type ii membrane protein, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 140810.40

Authors

Schiefner, A.,Deuschle, F.-C.,Skerra, A. (deposition date: 2019-09-13, release date: 2020-06-17, Last modification date: 2024-11-13)

Primary citation

Deuschle, F.C.,Schiefner, A.,Brandt, C.,Skerra, A.
Design of a surrogate Anticalin protein directed against CD98hc for preclinical studies in mice.
Protein Sci., 29:1774-1783, 2020

PubMed Abstract: The human CD98 heavy chain (CD98hc) offers a promising biomedical target both for tumor therapy and for drug delivery to the brain. We have previously developed a cognate Anticalin protein with picomolar affinity and demonstrated its effectiveness in a xenograft animal model. Due to the lack of cross-reactivity with the murine ortholog, we now report the development and X-ray structural analysis of an Anticalin with high affinity toward CD98hc from mouse. This binding protein recognizes the same protruding epitope loop-despite distinct structure-in the membrane receptor ectodomain as the Anticalin selected against human CD98hc. Thus, this surrogate Anticalin should be useful for the preclinical assessment of CD98hc targeting in vivo and support the translational development for medical application in humans.

PubMed: 32463547
DOI: 10.1002/pro.3894

Experimental method

X-RAY DIFFRACTION (2.75 Å)