Quantitative characterization of all single amino acid variants of a viral capsid-based drug delivery vehicle.


Self-assembling proteins are critical to biological systems and industrial technologies, but predicting how mutations affect self-assembly remains a significant challenge. Here, we report a technique, termed SyMAPS (Systematic Mutation and Assembled Particle Selection), that can be used to characterize the assembly competency of all single amino acid variants of a self-assembling viral structural protein. SyMAPS studies on the MS2 bacteriophage coat protein revealed a high-resolution fitness landscape that challenges some conventional assumptions of protein engineering. An additional round of selection identified a previously unknown variant (CP[T71H]) that is stable at neutral pH but less tolerant to acidic conditions than the wild-type coat protein. The capsids formed by this variant could be more amenable to disassembly in late endosomes or early lysosomes-a feature that is advantageous for delivery applications. In addition to providing a mutability blueprint for virus-like particles, SyMAPS can be readily applied to other self-assembling proteins.

Submission Details

ID: 2VxwaJVT

Submitter: Shu-Ching Ou

Submission Date: Dec. 20, 2018, 4:51 p.m.

Version: 1

Publication Details
Hartman EC;Jakobson CM;Favor AH;Lobba MJ;Álvarez-Benedicto E;Francis MB;Tullman-Ercek D,Nat Commun (2018) Quantitative characterization of all single amino acid variants of a viral capsid-based drug delivery vehicle. PMID:29643335
Additional Information

Study Summary

Number of data points 2452
Proteins Capsid protein
Unique complexes 2452
Assays/Quantities/Protocols Experimental Assay: Apparent Fitness Scores
Libraries Variants for Capsid Protein

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
300.0 A,B,C Capsid protein P03612 CAPSD_BPMS2
293.1 A,B,C Capsid protein P69170 CAPSD_BPR17
293.1 A,B,C Capsid protein P69171 CAPSD_BPZR
290.70000000000005 A,B,C Capsid protein P03611 CAPSD_BPF2