6VIT

The Crystal Structure of Apo Domain-Swapped dimer Q108K:T51D:I32C Variant of HCRBPII with an Engineered Disulfide Bond

Summary for 6VIT

• Entry DOI: 10.2210/pdb6vit/pdb
• Descriptor: Retinol-binding protein 2 (2 entities in total)
• Functional Keywords: domain swapped trimer, ilbp, lipid binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 31204.95

Authors

Ghanbarpour, A.,Geiger, J. (deposition date: 2020-01-13, release date: 2020-08-19, Last modification date: 2024-10-16)

Primary citation

Ghanbarpour, A.,Santos, E.M.,Pinger, C.,Assar, Z.,Hossaini Nasr, S.,Vasileiou, C.,Spence, D.,Borhan, B.,Geiger, J.H.
Human Cellular Retinol Binding Protein II Forms a Domain-Swapped Trimer Representing a Novel Fold and a New Template for Protein Engineering.
Chembiochem, 21:3192-3196, 2020

PubMed Abstract: Domain-swapping is a mechanism for evolving new protein structure from extant scaffolds, and has been an efficient protein-engineering strategy for tailoring functional diversity. However, domain swapping can only be exploited if it can be controlled, especially in cases where various folds can coexist. Herein, we describe the structure of a domain-swapped trimer of the iLBP family member hCRBPII, and suggest a mechanism for domain-swapped trimerization. It is further shown that domain-swapped trimerization can be favored by strategic installation of a disulfide bond, thus demonstrating a strategy for fold control. We further show the domain-swapped trimer to be a useful protein design template by installing a high-affinity metal binding site through the introduction of a single mutation, taking advantage of its threefold symmetry. Together, these studies show how nature can promote oligomerization, stabilize a specific oligomer, and generate new function with minimal changes to the protein sequence.

PubMed: 32608180
DOI: 10.1002/cbic.202000405

Experimental method

X-RAY DIFFRACTION (3.2 Å)