Typical structure of<unk> . NTS = N terminal segment. TMD = transmembrane domain. ATS = intracellular acidic terminal segment.<unk>  is a large family of proteins having high molecular weights ranging from 200 to 350 kDa. The wide range of molecular size reflects extreme variation in the amino acid composition of the proteins. But all the<unk>  proteins can be described as having three basic structural components, namely, an extracellular domain (ECD), a transmembrane domain (TMD) and an intracellular acidic terminal segment (ATS). The extracellular domain is fully exposed on the cell surface, and is the most variable region. It consists of a number of sub-domains, including a short and conserved N terminal segment (NTS) at the outermost region, followed by a highly variable Duffy-binding-like (DBL) domain, sometimes a Ca2+-binding C2 domain, and then one or two cysteine-rich interdomain regions (CIDRs). Duffy-binding-like domains are so named because of their similarity to the Duffy binding proteins of P. vivax and P. knowlesi. There are six variant types of DBL, named DBLα, DBLβ, DBLγ, DBLδ, DBLε and DBLζ. CIDR is also divided into three classes: CIDRα, CIDRβ and CIDRγ. Both DBL and CIDR have an additional type called PAM, so named because of their specific involvement in pregnancy-associated malaria (PAM). In spite of the diverse DBL and CIDR proteins, the extracellular amino terminal region is partly conserved, consisting of about 60 amino acids of NTS, one each of DBLα and CIDR1 proteins in tandem. This semi-conserved DBLα-CIDR1 region is called the head structure. The last CIDR region joins the TMD, which is embedded in the cell<unk> . The TMD and ATS are highly conserved among different<unk> s, and their structures have been solved using solution NMR (). The head structure is followed by a variable combination of diverse DBL and CIDR proteins, and in many cases along with C2. This variation gives rise to different types of<unk> . The DBL-CIDR combination in a particular type of<unk>  protein is never random, but organized into specific sequences known as domain cassettes. In some domain cassettes, there are only two or few DBL domains and CIDR domains, but in others they cover the entire length of the<unk> . These differences are responsible for different binding capacity among different<unk> s. For instance, among the most well-known types, VAR3 (earlier called type 3<unk>  is the smallest, consisting of only NTS with DBL1α and DBL2ε domains in the ECD. Its molecular size is approximately 150 kDa. In domain cassette (DC) 4 type, the ECD is made up of three domains DBLα1.1/1.4, CIDRα1.6 and DBLβ3. The DBLβ3 domain contains a binding site for intercellular adhesion molecule 1 (ICAM1). This is particularly implicated with the development of brain infection. VAR2CSA is atypical in having a single domain cassette that consists of three N terminal DBLPAM domains followed by three DBLε domains and one CIDRPAM. The seven domains always occur together. The usual NTS is absent. The protein specifically binds to chondroitin sulphate A (CSA); hence the name VAR2CSA.
Plasmodium falciparum erythrocyte membrane protein 1
Adenovirus E1B protein
M protein 
Tumor-associated glycoprotein 72
Penicillin-binding proteins
T independent antigen 
Lipopolysaccharide binding protein
Tax gene product