8SRN

De novo designed transmembrane antiparallel homo-dimer G-X6-G 01322-42

Summary for 8SRN

• Entry DOI: 10.2210/pdb8srn/pdb
• Descriptor: Gx6G_denovo_design_01322-42 (1 entity in total)
• Functional Keywords: homo-dimer, membrane protein, computational design, single-pass, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 6
• Total formula weight: 18976.83

Authors

Golden, J.,Dai, X.,Mravic, M. (deposition date: 2023-05-05, release date: 2024-09-04, Last modification date: 2026-02-11)

Primary citation

Golden, K.,Avarvarei, C.,Anderson, C.T.,Holcomb, M.,Tang, W.,Dai, X.,Zhang, M.,Mailie, C.A.,Sanchez, B.B.,Chen, J.S.,Forli, S.,Mravic, M.
Design principles of the common Gly-X6-Gly membrane protein building block.
Proc.Natl.Acad.Sci.USA, 122:e2503134122-e2503134122, 2025

PubMed Abstract: Protein behavior in lipids is poorly understood and inadequately represented in current computational models. Design and prediction abilities for bilayer-embedded molecular structures may be improved by characterizing membrane proteins' most frequent, favored structural features to glean both context-specific and general principles. We used protein design to proactively interrogate the sequence-structure relationship and stabilizing atomic details of two highly prevalent antiparallel transmembrane (TM) motifs with Small-X-Small consensus sequences. A fragment-based data-mining and sequence statistical inference method including cross-evolutionary structure-aligned covariance enabled engineering of de novo TM protein assemblies by successfully encoding Gly-X6-Gly and Ala-X6-Ala building blocks. A highly stable glycine-based design's X-ray structure hosts Cα-H∙∙∙O = C H-bonding alongside extensive backbone-directed van der Waals packing, idealizing features of this motif in Nature. Data-driven design navigates sequence space to directly inquire upon how to encode and stabilize vital membrane protein structural elements, facilitating efficacious construction of lipid-embedded architectures of increasing complexity.

PubMed: 41055983
DOI: 10.1073/pnas.2503134122

Experimental method

X-RAY DIFFRACTION (3.275 Å)