Three-dimensional structures of the free and the antigen-complexed Fab from monoclonal anti-lysozyme antibody D44.1

Braden, Bradford C.; Souchon, H.; Eiselé, Jean Luc; Bentley, G.A.; Bhat, Thirumaleshwara N.; Navaza, Jorge; Poljak, Roberto J.

doi:10.1016/0022-2836(94)90046-9

Cited by 143 publications

(119 citation statements)

References 42 publications

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“…Similar -stacking interactions have been observed in different antibody-antigen complexes (35) and other proteins (36). The interaction modes of aromatic side chains with the buckyball are also remarkably similar to those observed in the x-ray structure of a buckyball cocrystallized with benzene molecules (37).…”

Section: Resultssupporting

confidence: 61%

Molecular dynamics analysis of a buckyball–antibody complex

Noon

Kong

2002

Proc. Natl. Acad. Sci. U.S.A.

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This is a multinanosecond molecular dynamics study of a bio-nano complex formed by a carbon nanoparticle, a buckyball C60, and a biological molecule, an antibody, with high binding affinity and specificity. In the simulation, the ball is completely desolvated by the binding site of the antibody by means of a nearly perfect shape complementarity and extensive side-chain interactions, with the exception that about 17% of the surface is persistently exposed to solvent and could be used for functional derivatization. The interactions are predominantly hydrophobic, but significant polar interactions occur as well. There exists a rich body of various -stacking interactions. Aromatic side chains are involved in both double and triple stackings with the ball. Some ionic side chains, such as the guanidinium group of arginine, also form -stackings with the ball. The results suggest that -stackings are very efficient and common modes of biological recognition of -electron-rich carbon nanoparticles. Most importantly, the results demonstrate that, in general, an ordinary protein binding site, such as that of an antibody, can readily bind to a carbon nanoparticle with high affinity and specificity through recognition modes that are common in protein-ligand recognition. molecular dynamics simulation ͉ molecular recognition ͉ bio-nano conjugate ͉ -stackings I n 1985, a third allotropic form of carbon was discovered (1). The molecule was named Buckministerfullerene, commonly known as the buckyball, because of its geodesic structure (2). Six years later, the fullerene family was expanded with the discovery of nanotubes (3). Because of the unique structural properties associated with these molecules (4), there is great interest in using them in real-world applications (5-9), including integrating nanoparticles into biological systems, a fast-emerging field known as bio-nanotechnology. Examples of potential applications in bio-nanotechnology are transporting devices for drug delivery (10, 11), carriers of radioactive agents for biomedical imaging (12, 13), and templates for designing pharmaceutical agents, such as HIV type 1 protease inhibitors (8, 9), antioxidant (14-16), chemotactic agents (17), and neuroprotectants (18).However, to introduce artificial nanomaterials into living cells, one must deal with issues such as water solubility, biocompatibility, and biodegradability. This requires a comprehensive understanding of the interactions of nanomaterials with biological molecules such as proteins, nucleic acids, membrane lipids, and even water molecules. As in the studies of protein interactions (19,20), computer simulation techniques are very useful to investigate the interfacial properties of bio-nano systems, especially the dynamic, thermodynamic, and mechanical properties, at different spatial and temporal resolutions (21,22). One particularly interesting subject is the study of the interactions of nanoparticles within the binding sites of proteins, and optimizing the interactions for improved bio-nano recognition.Recent bio...

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Section: Resultssupporting

confidence: 61%

Molecular dynamics analysis of a buckyball–antibody complex

Noon

Kong

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…Only two nonglycyl residues in each Fab, V L Ala52 and V H Asp31, are in disallowed regions of a Ramachandran plot (data not shown). Similar occurrences in tight turns have been observed in other Fabs (27)(28)(29).…”

Section: Quality Of the Modelsupporting

confidence: 87%

“…The constant domains C H 1 from KAU (human IgM), HIL (human IgG1) (46), D44.1 (murine IgG1) (47) and Bv04 -01 (murine IgG2b) (48) were aligned by a least-squares superposition to compare the folding conservation among these isotypes. The ␣-carbon structure of the IgM KAU C H 1 domain is very similar to all other C H 1 domains analyzed (Fig.…”

Section: Constant Regionmentioning

confidence: 99%

Three-Dimensional Structure of the Fab from a Human IgM Cold Agglutinin

Cauerhff¹,

Braden

Carvalho

et al. 2000

The Journal of Immunology

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Cold agglutinins (CAs) are IgM autoantibodies characterized by their ability to agglutinate in vitro RBC at low temperatures. These autoantibodies cause hemolytic anemia in patients with CA disease. Many diverse Ags are recognized by CAs, most frequently those belonging to the I/i system. These are oligosaccharides composed of repeated units of N-acetyllactosamine, expressed on RBC. The three-dimensional structure of the Fab of KAU, a human monoclonal IgM CA with anti-I activity, was determined. The KAU combining site shows an extended cavity and a neighboring pocket. Residues from the hypervariable loops VHCDR3, VLCDR1, and VLCDR3 form the cavity, whereas the small pocket is defined essentially by residues from the hypervariable loops VHCDR1 and VHCDR2. This fact could explain the VH4-34 germline gene restriction among CA. The KAU combining site topography is consistent with one that binds a polysaccharide. The combining site overall dimensions are 15 Å wide and 24 Å long. Conservation of key binding site residues among anti-I/i CAs indicates that this is a common feature of this family of autoantibodies. We also describe the first high resolution structure of the human IgM CH1:CL domain. The structural analysis shows that the CH1-CL interface is mainly conserved during the isotype switch process from IgM to IgG1.

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“…The most studied antigen has been HEL, and there are now five structures reported for complexes with this antigen. They are D1.3 (12)(13)(14)(15), 69), HyHEL-10 (17), D11.15 (18), and D44.1 (19).…”

Section: Structures Of Complexes With Protein Antigensmentioning

confidence: 99%