scholarly journals Structural Diversity Problems and the Solving Method for Antibody Light Chains

2018 ◽  
Author(s):  
Emi Hifumi ◽  
Hiroaki Taguchi ◽  
Ryuichi Kato ◽  
Mitsue Arakawa ◽  
Yoshiki Katayama ◽  
...  
Keyword(s):  
Structural Diversity ◽  
Light Chains

Evidence for structural diversity in light chains of kappa type human cold agglutinins

1971 ◽  
Vol 8 (3) ◽  
pp. 265-269 ◽  
Author(s):  
Corrado Baglioni ◽  
Ralph C Williams
Keyword(s):  
Structural Diversity ◽  
Light Chains ◽  
Cold Agglutinins

Role of the constant region domain in the structural diversity of human antibody light chains

2017 ◽  
Vol 31 (4) ◽  
pp. 1668-1677 ◽  
Author(s):  
Emi Hifumi ◽  
Hiroaki Taguchi ◽  
Ryuichi Kato ◽  
Taizo Uda
Keyword(s):  
Structural Diversity ◽  
Light Chains ◽  
Human Antibody ◽  
Constant Region

scholarly journals Germline-Dependent Antibody Paratope States and Pairing Specific VH-VL Interface Dynamics

2021 ◽  
Vol 12 ◽  
Author(s):  
Monica L. Fernández-Quintero ◽  
Katharina B. Kroell ◽  
Lisa M. Bacher ◽  
Johannes R. Loeffler ◽  
Patrick K. Quoika ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Light Chain ◽  
Rational Design ◽  
Structural Diversity ◽  
Structural Features ◽  
Antibody Engineering ◽  
Light Chains ◽  
Interaction Patterns ◽  
Conformational Diversity ◽  
Key Aspects

Antibodies have emerged as one of the fastest growing classes of biotherapeutic proteins. To improve the rational design of antibodies, we investigate the conformational diversity of 16 different germline combinations, which are composed of 4 different kappa light chains paired with 4 different heavy chains. In this study, we systematically show that different heavy and light chain pairings strongly influence the paratope, interdomain interaction patterns and the relative VH-VL interface orientations. We observe changes in conformational diversity and substantial population shifts of the complementarity determining region (CDR) loops, resulting in distinct dominant solution structures and differently favored canonical structures. Additionally, we identify conformational changes in the structural diversity of the CDR-H3 loop upon different heavy and light chain pairings, as well as upon changes in sequence and structure of the neighboring CDR loops, despite having an identical CDR-H3 loop amino acid sequence. These results can also be transferred to all CDR loops and to the relative VH-VL orientation, as certain paratope states favor distinct interface angle distributions. Furthermore, we directly compare the timescales of sidechain rearrangements with the well-described transition kinetics of conformational changes in the backbone of the CDR loops. We show that sidechain flexibilities are strongly affected by distinct heavy and light chain pairings and decipher germline-specific structural features co-determining stability. These findings reveal that all CDR loops are strongly correlated and that distinct heavy and light chain pairings can result in different paratope states in solution, defined by a characteristic combination of CDR loop conformations and VH-VL interface orientations. Thus, these results have broad implications in the field of antibody engineering, as they clearly show the importance of considering paired heavy and light chains to understand the antibody binding site, which is one of the key aspects in the design of therapeutics.

Structure of Myosin Subfragment-1 from Electron Microscopy and Crystallography

1988 ◽  
Vol 46 ◽  
pp. 156-157
Author(s):  
Donald A. Winkelmann
Keyword(s):  
Electron Microscopy ◽  
Molecular Weight ◽  
Actin Filaments ◽  
Light Chains ◽  
Myosin Filament ◽  
Primary Role ◽  
Heavy Chains ◽  
Myosin Subfragment ◽  
Myosin Subfragment 1 ◽  
Globular Head

The primary role of the interaction of actin and myosin is the generation of force and motion as a direct consequence of the cyclic interaction of myosin crossbridges with actin filaments. Myosin is composed of six polypeptides: two heavy chains of molecular weight 220,000 daltons and two pairs of light chains of molecular weight 17,000-23,000. The C-terminal portions of the myosin heavy chains associate to form an α-helical coiled-coil rod which is responsible for myosin filament formation. The N-terminal portion of each heavy chain associates with two different light chains to form a globular head that binds actin and hydrolyses ATP. Myosin can be fragmented by limited proteolysis into several structural and functional domains. It has recently been demonstrated using an in vitro movement assay that the globular head domain, subfragment-1, is sufficient to cause sliding movement of actin filaments.The discovery of conditions for crystallization of the myosin subfragment-1 (S1) has led to a systematic analysis of S1 structure by x-ray crystallography and electron microscopy. Image analysis of electron micrographs of thin sections of small S1 crystals has been used to determine the structure of S1 in the crystal lattice.

Immunolabelling of glomerular deposits in kidney biopsies routinely fixed in glutaraldehyde

1989 ◽  
Vol 47 ◽  
pp. 910-911
Author(s):  
Ś Lhoták ◽  
I. Alexopoulou ◽  
G. T. Simon
Keyword(s):  
Uv Light ◽  
Kidney Diseases ◽  
Light Chains ◽  
Microscopical Level ◽  
Accurate Identification ◽  
Light Microscopical Level ◽  
Dense Deposits ◽  
Cacodylate Buffer ◽  
Glomerular Deposits ◽  
Prognostic Importance

Various kidney diseases are characterized by the presence of dense deposits in the glomeruli. The type(s) of immunoglobulins (Igs) present in the dense deposits are characteristic of the disease. The accurate Identification of the deposits is therefore of utmost diagnostic and prognostic importance. Immunofluorescence (IF) used routinely at the light microscopical level is unable to detect and characterize small deposits found in early stages of glomerulonephritis. Although conventional TEM is able to localize such deposits, it is not capable of determining their nature. It was therefore attempted to immunolabel at EM level IgG, IgA IgM, C3, fibrinogen and kappa and lambda Ig light chains commonly found in glomerular deposits on routinely fixed ( 2% glutaraldehyde (GA) in 0.1M cacodylate buffer) kidney biopsies.The unosmicated tissue was embedded in LR White resin polymerized by UV light at -10°C. A postembedding immunogold technique was employed

Metal-, and Organocatalyst-Free One-Pot Assembly of Chiral Aza-Tricyclic Molecules: Creating Six Contiguous Stereocenters from 2-D-Structures and an Amino Acid

2020 ◽  
Author(s):  
Dung Do
Keyword(s):  
Amino Acid ◽  
Chemical Space ◽  
Structural Diversity ◽  
Therapeutic Agents ◽  
Chiral Molecules ◽  
One Pot ◽  
Complex Molecules ◽  
Chiral Catalyst ◽  
Chiral Complex ◽  
Free Process

<p>Chiral molecules with their defined 3-D structures are of paramount importance for the study of chemical biology and drug discovery. Having rich structural diversity and unique stereoisomerism, chiral molecules offer a large chemical space that can be explored for the design of new therapeutic agents.<sup>1</sup> Practically, chiral architectures are usually prepared from organometallic and organocatalytic processes where a transition metal or an organocatalyst is tailor-made for desired reactions. As a result, developing a method that enables rapid assembly of chiral complex molecules under metal- and organocatalyst-free condition represents a daunting challenge. Here we developed a straightforward route to create a chiral 3-D structure from 2-D structures and an amino acid without any chiral catalyst. The center of this research is the design of a <a>special chiral spiroimidazolidinone cyclohexadienone intermediate</a>, a merger of a chiral reactive substrate with multiple nucleophillic/electrophillic sites and a transient organocatalyst. <a>This unique substrate-catalyst (“subcatalyst”) dual role of the intermediate enhances </a><a>the coordinational proximity of the chiral substrate and catalyst</a> in the key Aza-Michael/Michael cascade resulting in a substantial steric discrimination and an excellent overall diastereoselectivity. Whereas the “subcatalyst” (hidden catalyst) is not present in the reaction’s initial components, which renders a chiral catalyst-free process, it is strategically produced to promote sequential self-catalyzed reactions. The success of this methodology will pave the way for many efficient preparations of chiral complex molecules and aid for the quest to create next generation of therapeutic agents.</p>

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