Entangled Motifs in Membrane Protein Structures

Area of Science:

• Structural biology
• Biophysics
• Computational biology

Background:

• Entangled motifs are observed in about one-third of globular protein structures.
• These motifs are linked to co-translational folding processes.
• Understanding their prevalence in membrane proteins is crucial.

Purpose of the Study:

• To investigate the presence and characteristics of entangled motifs in membrane protein structures.
• To compare entangled motif properties between membrane and globular proteins.
• To explore the influence of co-translational folding on membrane protein structure.

Main Methods:

• Construction of a non-redundant dataset of membrane protein domains from existing databases.
• Annotation of membrane proteins with labels such as monotopic/transmembrane and peripheral/integral.
• Evaluation of entangled motifs using the Gaussian entanglement indicator.

Main Results:

• Entangled motifs were found in one-fifth of transmembrane and one-fourth of monotopic proteins.
• The distribution of entanglement indicator values in membrane proteins mirrors that of globular proteins.
• Chirality bias for single-winding motifs is consistent, but reversed for double-winding motifs in membrane proteins compared to globular proteins.

Conclusions:

• Entangled motifs are prevalent in membrane proteins, with distributions similar to globular proteins.
• Differences in chirality bias for double-winding motifs suggest unique co-translational folding mechanisms in membrane proteins.
• Co-translational biogenesis machinery imposes distinct constraints on membrane versus globular protein folding.