4JG0: Structure of phosphoserine/threonine (pSTAb) scaffold bound to pSer peptide

Citation:
Abstract
Aberrant changes in post-translational modifications (PTMs) such as phosphate groups underlie a majority of human diseases. However, detection and quantification of PTMs for diagnostic or biomarker applications often require PTM-specific monoclonal antibodies (mAbs), which are challenging to generate using traditional antibody-selection methods. Here we outline a general strategy for producing synthetic, PTM-specific mAbs by engineering a motif-specific 'hot spot' into an antibody scaffold. Inspired by a natural phosphate-binding motif, we designed and selected mAb scaffolds with hot spots specific for phosphoserine, phosphothreonine or phosphotyrosine. Crystal structures of the phospho-specific mAbs revealed two distinct modes of phosphoresidue recognition. Our data suggest that each hot spot functions independently of the surrounding scaffold, as phage display antibody libraries using these scaffolds yielded >50 phospho- and target-specific mAbs against 70% of target peptides. Our motif-specific scaffold strategy may provide a general solution for rapid, robust development of anti-PTM mAbs for signaling, diagnostic and therapeutic applications.
PDB ID: 4JG0Download
MMDB ID: 113016
PDB Deposition Date: 2013/2/28
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.81  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 4JG0: trimeric; determined by author and by software (PISA)
Molecular Components in 4JG0
Label Count Molecule
Proteins (3 molecules)
1
FAB Light Chain
Molecule annotation
1
FAB Heavy Chain
Molecule annotation
1
Phosphopeptide
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.