Ca1.1 voltage-sensing domain III exclusively controls skeletal muscle excitation-contraction coupling.

Skeletal muscle contractions are initiated by action potentials, which are sensed by the voltage-gated calcium channel (Ca1.1) and are conformationally coupled to calcium release from intracellular stores. Notably, Ca1.

Surprisingly Fast Interface and Elbow Angle Dynamics of Antigen-Binding Fragments.

Fab consist of a heavy and light chain and can be subdivided into a variable (V and V ) and a constant region (C 1 and C ). The variable region contains the complementarity-determining region (CDR), which is formed by six hypervariable loops, shaping the antigen binding site, the paratope. Apart from the CDR loops, both the elbow angle and the relative interdomain orientations of the V -V and the C 1-C domains influence the shape of the paratope.

Antibody CDR loops as ensembles in solution vs. canonical clusters from X-ray structures.

In the past decade, the relevance of antibodies as therapeutics has increased substantially. Therefore, structural and functional characterization, in particular of the complementarity-determining regions (CDRs), is crucial to the design and engineering of antibodies with unique binding properties. Various studies have focused on classifying the CDR loops into a small set of main-chain conformations to facilitate antibody design by assuming that certain sequences can only adopt a limited number of conformations.

Antibody humanization-the Influence of the antibody framework on the CDR-H3 loop ensemble in solution.

Antibody engineering of non-human antibodies has focused on reducing immunogenicity by humanization, being a major limitation in developing monoclonal antibodies. We analyzed four series of antibody binding fragments (Fabs) and a variable fragment (Fv) with structural information in different stages of humanization to investigate the influence of the framework, point mutations and specificity on the complementarity determining region (CDR)-H3 loop dynamics. We also studied a Fv without structural information of the anti-idiotypic antibody Ab2/3H6, because it completely lost its binding affinity upon superhumanization, as an example of a failed humanization.