What type of antibody is a dimer

Heavy chains are bound to light chains by sulfhydryl linkages to form a Y shaped structure. The stem of the Y contains the constant region Fc and the two prongs of the Y contain the variable region Fab.

The Fab interacts with the antigen and therefore is unique to each antibody, while the Fc is common to all antibodies and interacts with the immune system.

The classes differ in their biological properties, otherwise known as effector functions, and their functional localization to ensure an appropriate immune response for a given antigen.

IgG provides the majority of antibody-based immunity against pathogens. Create mode — the default mode when you create a requisition and PunchOut to Bio-Rad. You can create and edit multiple shopping carts. Edit mode — allows you to edit or modify an existing requisition prior to submitting. You will be able to modify only the cart that you have PunchedOut to, and won't have access to any other carts.

Inspect mode — when you PunchOut to Bio-Rad from a previously created requisition but without initiating an Edit session, you will be in this mode. You cannot modify any Cart contents. Click here to find out how. Plotting the CD value at nm against temperature suggested a two phase denaturation Fig. Gr6 is a dimeric protein of amino-acid residues and the crystal structure has been solved to 1.

The majority of the electron density is well-defined which allows for unambiguously model building. The first three residues at the N-terminus in monomer A and the first four residues in monomer B are disordered in the map. In addition, the C-terminus of the last 12 residues in monomer A and 13 residues in monomer B, as well as the 6xHIS tag, could not be traced in the map.

Kabat nomenclature [19] is used to number the positions of the amino acids and for the description of the structure. The crystallographic analysis showed that two molecules are present in the asymmetric unit in which one molecule is related to the other by a non-crystallographic 2-fold axis to form a dimer.

The refined model includes residues Val2-Gly in monomer A and residues Gln3-Ser in monomer B as well as water molecules. Validation of the structure by program SFCHECK [20] showed that the refined model is of good stereochemical quality Table 1 and that no phi-psi angles are in the disallowed regions of the Ramachandran map.

A Ribbon diagram of the Gr6 structure shown in cyan chain A and red chain B. CDRs are colored in green in chain A and orange in chain B. Superimposition Fig. A unique feature of the Gr6 structure is that CDR3 protrudes beyond the boundary of dimer interface and points to the other side of the other monomer.

Polar interaction in the interface includes 9 direct hydrogen bonds. No salt bridges and water molecules are found throughout the interface.

Single-domain antibodies are very attractive tumor-targeting tools for their natural properties of small size, solubility and high permeability into tissues. An important feature of camelid sdAbs is their high thermodynamic stability [8]. This feature not only contributes to the high expression yield, but may also be required for their in vivo tumor targeting ability [25]. Therefore, we presume that these human sdAb are as stable as camelid sdAb.

The single domain antibodies are also known for their monomeric behavior. In solution, Gr3 exists as a monomer; however, Gr6 has an unusual nature of being a strict dimer. To our knowledge, Gr6 is the first sdAb derived from human V H with this characteristics and the solved crystal structure of Gr6 presented here is the first structure of human sdAb with a dimeric conformation.

The crystallographic data presented here shows that Gr6 exists as a homodimer, consistent with the SEC analysis result. Among those residues, Val37, Leu45, Trp47, Ala50, Trp are the hall mark residues situated at the V H -V L heterodimer interface of the immunologlobulin variable domain [19] , [26] , [27]. One Gr6 monomer is shown in cyan and the other one is shown in gray.

B Surface representation of V H. Residues involved in dimer formation are highlighted in yellow. The first three amino acids, Val37, Leu45 and Trp47 are substituted to Phe37, Arg45 and Gly47 in camelid V H H and are considered to be hallmark substitutions that make these sdAbs more soluble [28] , [29]. However, Gr3 which contains all of these three hydrophobic residues is monomeric and soluble. This suggests that these residues play essential roles in Gr6 dimer formation and replacement of these residues in Gr3 LeuPro, ProGlu, LeuGln, AlaArg disrupts the inter-domain interaction.

This result provides at least an exception of the suggestion that solubility and stability of V H is independent of the CDR3 sequence [16]. The dimerization of cV H -E2 should be the consequence of the selected CDR3 loop because the molecule was affinity-selected from a library in which CDR3 is randomized, implying that CDR3 should be involved in the dimerization [21].

However, in the crystal structure of cV H -E2 dimer, the CDR3 loops are at the opposite sides of the molecule and do not participate in the inter-domain interaction [21].

Therefore, the crystallographic structure of cV H -E2 is probably a result of crystal packing and may not represent the observed dimer in solution. In this work, the Gr6 crystal structure shows that the V H -V H interface mimics the classical association of V H -V L dimer, strongly suggesting that Gr6 is a strict dimer and that the structure does represent the dimerization in solution.

The Gr6 structure present here not only provides information on how the dimer is associated, but also confirms that the dimerization of the sdAb cannot avoid the traditional V L -binding interface. Although trastuzumab Herceptin, Genentech Inc. One of the problems with trastuzumab is that it does not efficiently block HER2 from dimerizing with other HER family members.

Therefore, Gr3 and Gr6 could be alternative HER2-targeted antibodies that possess the advantage of accessibility to hidden antigens that are not easily reached by whole antibodies. The characterization and structural information obtained in this work therefore will be beneficial to the future design of such humanized sdAbs in the HER2-dependent cancer therapy. The synthetic phagemid-based human V H library used in this study has been previously described [15] , [17].

V H repertoire was expressed on phage after infection with M13K07 helper phage as described [18]. Like IgM, the multimeric form of IgA contains a tail piece at the carboxy terminus and is held together by the J chain.

The secretory component is a 75 kDa polypeptide chain synthesised by epithelial cells of the gut for linkage to the dimeric form of IgA.

As the name implies the secretory component facilitates IgA transport across epithelial cells but is also involved in protecting IgA secreted into the lumen of the gut from proteolytic digestion.

IgD has the same basic structure as IgG but with an extended hinge region which is very susceptible to proteolytic digestion. The precise function of this class of antibody is still unknown.

IgE is very scarce in the serum but is found on the basophils and mast-cells of all individuals 1.