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Updated: Jan 7, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

キラル反転変異誘発法による自己会合型低複雑性ドメイン内の幾何学的に制約された残基の同定

Ryan L Beckner¹, Christien Carter¹, Glen Liszczak¹

¹Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA.

bioRxiv : the preprint server for biology

|December 25, 2025

Abstract:

Many protein low-complexity domains (LCDs) reversibly self-associate to enable cellular function, yet fundamental questions remain regarding how polypeptide chemical and structural features beyond side chain identity contribute to LCD-LCD interactions. For instance, the folds adopted by globular proteins emerge from constraints enforced by homo-chirality of genetically-encoded polypeptides. However, it remains unclear to what extent similar geometric constraints apply to LCD self-association. Herein, we use protein total- and semi-synthesis to probe the contribution of C^α stereochemistry to LCD self-association with synthetic Chiral Inversion Mutagenesis (ChIM). By introducing targeted L-to-D amino acid inversions, ChIM identifies C^α stereocenters under geometric constraint without modification of side-chain functionalities. We apply ChIM to the LCDs of inner nuclear lamina protein Emerin and neurofilament light chain and find that chiral inversion produces strongly position-dependent effects upon LCD self-association. Our study describes essential structural features that enable LCD self-association and chemical strategies to interrogate LCD biochemistry.

キーワード:

低複雑性ドメインキラル反転変異誘発法タンパク質オリゴマー化自己会合合成タンパク質化学

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Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins

Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins

Published on: September 23, 2021

Identification of Functional Protein Regions Through Chimeric Protein Construction

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Published on: January 8, 2019

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Chirality in Nature

Chirality in Nature

Chirality is the most intriguing yet essential facet of nature, governing life’s biochemical processes and precision. It can be observed from a snail shell pattern in a macroscopic world to an amino acid, the minutest building block of life. Most of the snails around the world have right-coiled shells because of the intrinsic chirality in their genes. All the amino acids present in the human body exist in an enantiomerically pure state, except for glycine - the sole achiral amino acid.

Conserved Binding Sites

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

Conserved Binding Sites

Conserved Binding Sites

Chirality at Nitrogen, Phosphorus, and Sulfur

Chirality at Nitrogen, Phosphorus, and Sulfur

Chirality is most prevalent in carbon-based tetrahedral compounds, but this important facet of molecular symmetry extends to sp3-hybridized nitrogen, phosphorus and sulfur centers, including trivalent molecules with lone pairs. Here, the lone pair behaves as a functional group in addition to the other three substituents to form an analogous tetrahedral center that can be chiral.
A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all...

Molecules with Multiple Chiral Centers

Molecules with Multiple Chiral Centers

Molecules that possess multiple chiral centers can afford a large number of stereoisomers. For instance, while some molecules like 2-butanol have one chiral center, defined as a tetrahedral carbon atom with four different substituents attached, several molecules like butane-2,3-diol have multiple chiral centers. A simple formula to predict the number of stereoisomers possible for a molecule with n chiral centers is 2n. However, there can be a lower number where some of the stereoisomers are...

Chirality

Chirality

Chirality is a term that describes the lack of mirror symmetry in an object. In other words, chiral objects cannot be superposed on their mirror images. For example, our feet are chiral, as the mirror image of the left foot, the right foot, cannot be superposed on the left foot.
Chiral objects exhibit a sense of handedness when they interact with another chiral object. For example, our left foot can only fit in the left shoe and not in the right shoe. Achiral objects — objects that have...