Cysteine-rich mini-proteins in human biology

Lavergne, Vincent, Taft, Ryan J. and Alewood, Paul F. (2012) Cysteine-rich mini-proteins in human biology. Current Topics in Medicinal Chemistry, 12 14: 1514-1533. doi:10.2174/156802612802652411

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Author Lavergne, Vincent
Taft, Ryan J.
Alewood, Paul F.
Title Cysteine-rich mini-proteins in human biology
Journal name Current Topics in Medicinal Chemistry   Check publisher's open access policy
ISSN 1568-0266
Publication date 2012-07-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2174/156802612802652411
Volume 12
Issue 14
Start page 1514
End page 1533
Total pages 20
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Language eng
Abstract Understanding the relationship between structure and function underpins both biochemistry and chemical biology, and has enabled the discovery of numerous agricultural and therapeutic agents. Small cysteine-rich proteins, which form a unique set of protein frameworks and folds, are found in all living organisms and often play crucial roles as hormones, growth factors, ion channel modulators and enzyme inhibitors in various biological pathways. Here we review secreted human cysteine-rich mini-proteins, classify them into broad families and briefly describe their structure and function. To systematically investigate this protein sub-class we designed a step-wise high throughput algorithm that is able to isolate the mature and active forms of human secreted cysteine-rich proteins (up to 200 amino acids in length) and extract their cysteine scaffolds. We limited our search to frameworks that contain an even number of cysteine residues (< 20), all of which are engaged in intra-molecular disulfide bonds. We found 53 different cysteine-rich frameworks spread over 378 secreted cysteine-rich mini-proteins. Restricting our search to those that contain >5% cysteine residues led to the identification of 22 cysteine-rich frameworks representing 21 protein families. Analysis of their molecular targets showed that these mini-proteins are frequently ligands for G protein- and enzyme-coupled receptors, transporters, extracellular enzyme inhibitors, and antimicrobial peptides. It is clear that these human secreted mini-proteins possess a wide diversity of frameworks and folds, some of which are conserved across the phylogenetic spectrum. Further study of these proteins will undoubtedly lead to insights into unresolved questions of basic biology, and the development of system-specific human therapeutics.
Keyword Cysteine framework
Cysteine scaffold
Cysteine-rich peptides
Cysteine-rich proteins
Secreted human mini-proteins
Structure-function relationship
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
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