Cis-nonProline peptides: Genuine occurrences and their functional roles
Jane S Richardson1, Lizbeth L Videau1, Christopher J Williams1
1Department of Biochemistry, Duke University, Durham, North Carolina, USA.
Summary
Cis-nonPro peptides are rare but functionally critical in protein structures, often found in carbohydrate-processing enzymes. Rigorous analysis confirms their genuine occurrences and biological importance.
Area of Science:
- Structural Biology
- Biochemistry
Background:
- Cis peptides before proline are common (5%), but cis peptides before other residues (cis-nonPro) are rare in protein structures.
- Genuine cis-nonPro occurrences are vital for biological functions, including enzyme active sites and disulfide bonds.
- Unjustified cis-nonPro assignments were frequent due to weak electron density in crystallographic data (2006-2015).
Purpose of the Study:
- To identify genuine cis-nonPro occurrences using high-resolution crystallographic data and stringent quality filtering.
- To survey the functional roles and structural contexts of identified cis-nonPro peptides.
- To highlight previously underemphasized aspects of cis-nonPro, such as their association with well-ordered structures and carbohydrate-related proteins.
Main Methods:
- Utilized high-resolution crystallographic data.
- Applied stringent quality-filtering at the residue level to minimize false positives.
- Analyzed a large sample of genuine cis-nonPro examples to identify functional and structural patterns.
Main Results:
- Developed a procedure to identify genuine cis-nonPro with high accuracy.
- Surveyed diverse functional roles and structural contexts of cis-nonPro.
- Observed that cis-nonPro predominantly occurs in well-ordered protein structures (except for vicinal disulfides).
- Found a significant concentration of cis-nonPro in proteins involved in carbohydrate processing or binding (CAZy database).
Conclusions:
- Genuine cis-nonPro peptides are rare but crucial for specific biological functions.
- Stringent data filtering is essential for accurate identification of cis-nonPro.
- Cis-nonPro peptides are strongly associated with well-ordered structures and carbohydrate-related proteins.
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