This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What are protein domains?
Protein domains are functional and/or structural units[1]. They are usually responsible for a specific interaction or function, which contribute to the overall function of the protein. Similar domains can be found in proteins with different overall functions.
Domains of lactase
What is the glycosyl hydrolase family 1?
The glycosyl hydrolase family 1 is part of the broad family of O-glycosyl hydrolases[2]. These enzymes hydrolyze(break) the glycosidic bonds between carbohydrates. Glycosyl hydrolase family 1 contains enzymes with many functions including: beta-glucosidase, beta-galactosidase, and lactase-phlorizin hydrolase (lactase).
What are the protein domains in the lactase homologs?
Which domains do CLD mutations affect?
Figure 6. This figure shows the different known mutation in LCT and how they affect the lactase protein. Mutations shown on top cause premature stop codons (truncated proteins), while mutations shown on bottom result in single amino acid substitutions. There is significant clustering of mutations affecting the fourth glycosyl hydolase family 1 domain, which is conserved in mature lactase and is critical to proper enzyme function.
Conclusions
Lactase has four domains, which are all from the glycosyl-hydrolase family 1. This domain functions in the cleavage of o-glycosyl bonds, which follows the expectations knowing the function of the lactase enzyme. Lactase breaks down lactose into its two monomers, which involves the cleavage of the glycosyl bond that joins them. Mutations in this domain would be useful to study, to elucidate how single amino acid mutations in the c-terminal glycosyl hydrolase domain can cause CLD pathogenicity.
References
[1] Protein Classification: an introduction to EMBL-EBI resources. www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[2] Glycoside hydrolase family 1. Protein sequence analysis and classification. www.ebi.ac.uk/interpro/entry/IPR001360
Header image: en.wikipedia.org/wiki/Structural_genomics#/media/File:Argonne%27s_Midwest_Center_for_Structural_Genomics_deposits_1,000th_protein_structure.jpg
[1] Protein Classification: an introduction to EMBL-EBI resources. www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[2] Glycoside hydrolase family 1. Protein sequence analysis and classification. www.ebi.ac.uk/interpro/entry/IPR001360
Header image: en.wikipedia.org/wiki/Structural_genomics#/media/File:Argonne%27s_Midwest_Center_for_Structural_Genomics_deposits_1,000th_protein_structure.jpg