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Antigen binding by antibodies requires precise orientation of the complementaritydetermining region (CDR) loops in the variable domain to establish the correct contact surface. Members of the family Camelidae have a modified form of immunoglobulin gamma (IgG) with only heavy chains, called Heavy Chain only Antibodies (HCAb). Antigen binding in HCAbs is mediated by only three CDR loops from the single variable domain (VHH) at the N-terminus of each heavy chain. This feature of the VHH, along with their other important features, e.g., easy expression, small size, thermo-stability and hydrophilicity, made them promising candidates for therapeutics and diagnostics. Thus, to design better VHH domains, it is important to thoroughly understand their sequence and structure characteristics and relationship. In this study, sequence characteristics of VHH domains have been analysed in depth, along with their structural features using innovative approaches, namely a structural alphabet. An elaborate summary of various studies proposing structural models of VHHdomains showed diversity in the algorithms used. Finally, a case study to elucidate the differences in structural models from single and multiple templates is presented. In this case study, along with the above-mentioned aspects of VHH, an exciting view of various factors in structure prediction of VHH, like template framework selection, is also discussed. [ABSTRACT FROM AUTHOR]

The development of single-cell RNA sequencing (scRNA-seq) technologies has greatly contributed to deciphering the tumor microenvironment (TME). An enormous amount of independent scRNA-seq studies have been published representing a valuable resource that provides opportunities for meta-analysis studies. However, the massive amount of biological information, the marked heterogeneity and variability between studies, and the technical challenges in processing heterogeneous datasets create major bottlenecks for the full exploitation of scRNA-seq data. We have developed IMMUcan scDB (https://immucanscdb.vital-it.ch), a fully integrated scRNA-seq database exclusively dedicated to human cancer and accessible to nonspecialists. IMMUcan scDB encompasses 144 datasets on 56 different cancer types, annotated in 50 fields containing precise clinical, technological, and biological information. A data processing pipeline was developed and organized in four steps: (i) data collection; (ii) data processing (quality control and sample integration); (iii) supervised cell annotation with a cell ontology classifier of the TME; and (iv) interface to analyze TME in a cancer type-specific or global manner. This framework was used to explore datasets across tumor locations in a gene-centric (CXCL13) and cell-centric (B cells) manner as well as to conduct meta-analysis studies such as ranking immune cell types and genes correlated to malignant transformation. This integrated, freely accessible, and user-friendly resource represents an unprecedented level of detailed annotation, offering vast possibilities for downstream exploitation of human cancer scRNA-seq data for discovery and validation studies., Significance: The IMMUcan scDB database is an accessible supportive tool to analyze and decipher tumor-associated single-cell RNA sequencing data, allowing researchers to maximally use this data to provide new insights into cancer biology., (©2022 The Authors; Published by the American Association for Cancer Research.)

Antigen binding by antibodies requires precise orientation of the complementarity- determining region (CDR) loops in the variable domain to establish the correct contact surface. Members of the family Camelidae have a modified form of immunoglobulin gamma (IgG) with only heavy chains, called Heavy Chain only Antibodies (HCAb). Antigen binding in HCAbs is mediated by only three CDR loops from the single variable domain (V H H) at the N-terminus of each heavy chain. This feature of the V H H, along with their other important features, e.g., easy expression, small size, thermo-stability and hydrophilicity, made them promising candidates for therapeutics and diagnostics. Thus, to design better V H H domains, it is important to thoroughly understand their sequence and structure characteristics and relationship. In this study, sequence characteristics of V H H domains have been analysed in depth, along with their structural features using innovative approaches, namely a structural alphabet. An elaborate summary of various studies proposing structural models of V H H domains showed diversity in the algorithms used. Finally, a case study to elucidate the differences in structural models from single and multiple templates is presented. In this case study, along with the above-mentioned aspects of V H H, an exciting view of various factors in structure prediction of V H H, like template framework selection, is also discussed., Competing Interests: Frederic Cadet is associated with PEACCEL, Paris, France. Jean-Christophe Gelly and Alexandre G. de Brevern are associated with IBL, Paris, France. Jean-Philippe Meyneil is employed by ISoft, Paris, France. Alain Malpertuy is employed by Atragene, Paris, France. Nicolas K. Shinada is sponsored by Discngine, Paris, France and ANRT, France. All other authors declare no competing interests., (©2020 Melarkode Vattekatte et al.)

Protein structures are valuable tools to understand protein function. Nonetheless, proteins are often considered as rigid macromolecules while their structures exhibit specific flexibility, which is essential to complete their functions. Analyses of protein structures and dynamics are often performed with a simplified three-state description, i.e., the classical secondary structures. More precise and complete description of protein backbone conformation can be obtained using libraries of small protein fragments that are able to approximate every part of protein structures. These libraries, called structural alphabets (SAs), have been widely used in structure analysis field, from definition of ligand binding sites to superimposition of protein structures. SAs are also well suited to analyze the dynamics of protein structures. Here, we review innovative approaches that investigate protein flexibility based on SAs description. Coupled to various sources of experimental data (e.g., B-factor) and computational methodology (e.g., Molecular Dynamic simulation), SAs turn out to be powerful tools to analyze protein dynamics, e.g., to examine allosteric mechanisms in large set of structures in complexes, to identify order/disorder transition. SAs were also shown to be quite efficient to predict protein flexibility from amino-acid sequence. Finally, in this review, we exemplify the interest of SAs for studying flexibility with different cases of proteins implicated in pathologies and diseases.