Creative Biolabs provides the best service for high affinity WW domain library construction. With our special Hi-Affi™ scaffold library construction platform, scientists of Creative Biolabs can obtain scaffold libraries with 100% precise mutant and over 1010 diversity.
WW domain, a peptide-binding motif with around 38 amino acids, is one of the smallest protein modules found in signaling and regulatory proteins which mediate the interactions of two proteins with each other. The structure of WW domain is distinctive, which is recognized as one of the simplest natural β-sheet structure. The structure analysis indicates that the WW domain has two highly conserved tryptophans separated by 20-22 amino acids, while the central section always includes an aromatic amino acid, and a strictly conserved proline is at the position 12 in relation to the second tryptophan. It also contains a small hydrophobic pocket formed by three antiparallel β-sheets, which can bind polyproline-rich motifs.
WW domain can be mainly divided into three groups based on their binding specificity. Group I is the one that interact with the core sequence PPxY (x can be any amino acid), like Yes-associated protein (YAP), WW1, and WW2 domains. Group II, such as FE65 WW domain, can proximate PPLP motif by binding a long stretch of prolines. Group III, such as FBP21 WW1 and WW2 domains, can interact with the PGM motif, which is a repeated polyproline-rich region containing glycine and methionine. Meanwhile, the searching for the specific ligand for WW domain is important in shedding lights on the disease mechanisms. For example, the loss of interaction between selected WW domains and their ligands could lead to Alzheimer’s disease. In this way, the plasticity of WW domain scaffold is considered to allow binding sites to be interchanged between different domains to confer different levels of binding specificity.
With years of effort in technical maturation, Creative Biolabs has developed the proprietary Hi-Affi™ phage display platform. This platform is based on the traditional phage display technology, which fuses the library of interest to bacteriophage coat proteins and thereby displayed on the phage surface to isolate specific binders. On top of that the Hi-Affi™ platform also combines with trimer codon technology and NNK method to improve the diversity and affinity of constructed scaffold libraries. This platform, therefore, is more suitable for sorting and isolating the high affinity protein or peptide targets.
Our most devoted researchers from Creative Biolabs have extensive experience in the field of scaffold library construction. Up to now, we have successfully provided our global customers for more than 50 kinds of scaffold libraries. Our scientists are enthused in providing high quality and efficient service to meet all customers’ specifications.
Fig. 1 Prototype WW domain. (PDB ID: 1E0M)