Analysis of Tertiary Order Structure by Cryogenic Electron Microscopy (cryo-EM) (CAT#: STEM-B-0379-CJ)

Introduction

Structure and conformation of a biological molecule is key for its function. The higher order structure of a biopharmaceutical molecule is, thereby, often directly connected to the quality, stability, safety, and efficacy of a therapy. The higher order structure is considered a critical quality attribute and, thus, a detailed understanding of the higher order structure of a biopharmaceutical compound is critical in every research and development phase. Characterizing the secondary, tertiary and, if present, quaternary structure of a biopharmaceutical compound requires multiple analytical techniques.<br /><br />The overall three-dimensional conformation of a single polypeptide chain (a protein molecule) is referred to as the tertiary structure, which typically includes different elements of secondary structures such as α helices, β sheets, random coils, and loops. Bonds between side chains (R groups) of amino acids—including hydrophobic interactions, hydrogen bonds, and ionic bonds —contribute to the tertiary structure.<br /><br />In addition, there is one type of covalent bond that can also contribute to tertiary structure: the disulfide bond. Disulfide bonds are a type of post-translational modification (PTM) formed between sulfur-containing side chains of cysteine residues, allowing distant parts of the protein to be held together. They are abundantly found in secretory proteins and extracellular domains of membrane proteins.