C1orf41 Discussion

Based on Blast, it was shown that this protein has high similarity sequence with small heat shock proteins (sHsp) from various eukaryotes. Our protein was a mutant of sHsp family B member 11 where aspartic acid at position 109 has been deleted. The first ten residues were believed not to be part of the protein but most likely an N-terminal histidine tag used during purification of the protein. This was proven by the multiple sequence alignment as these residues does not align with other organisms. Therefore, there is a possibility that c1orf41 may be a sHsp.

sHsp are molecular chaperones that can be found in various organisms, however their sequence poorly conserved. Studies have shown that the number of gene encoding sHsp increases in higher eukaryote. This may due to the specific function and localization of sHsp (Haslbeck et al., 2005). Since it was shown to be highly expressed in cancer cell, the function of this protein may be related to cancer. The loss of Asp109 may cause cancer or cancer cells produce this mutated protein.

As for the structure of the protein, we found that c1orf41 has a jelly-roll fold which is characteristic of a discoidin domain member. The Pfam and DALI result also showed that this protein has a discoidin domain, specifically the F5/8 type C domain. F5/8 type C domain is involved in cell-cell interaction and cell recognition. Highly expressed, the protein can lead to breast carcinoma.

Discoidin domain is usually found in proteins that bind galactose. This property was shown in many of the proteins from the DALI result. Based on this it is likely that c1orf41 may have galactose binding characteristic as well. From previous literatures ..... are the residues important for galactose binding...... However they Even though the structure showed similarity with galactose binding domain, the binding site of galactose was not found in c1orf41. This indicates that this protein does not bind to galactose. The proteins from the DALI result showed minimal sequence similarity with c1orf41.

During evolution, cells have been developing complex mechanisms to respond many physiological and environmental stresses. One protein which its expressions correlate with stress response is small heat shock protein (Concannon & Samali, 2003).In normal condition (unstressed condition), sHsps are known to have chaperone function which prevent protein aggregation induced by thermal and chemical stress (Bellyei et al., 2006).The expression of Hsp is cytoprotective, which is protecting cells from stress and preventing their deaths. Hsps will bind to the damaged misfolded polypeptides and mediate the refolding, thus it will protect cells from harmful effects and promote cell recovery (concannon & Samali, 2003).

Many publication also reported that sHsps have antiapoptotic activity which if over expressed will lead to tumor growth and resistance to chemo or radiotheraphy (Bellyei et al, 2006; Pozsgai et al, 2007). The stimulation of apoptosis was activated by one or more transduction pathway signal which then will activate a conserved family of aspartic-acid specific cysteine protease (caspase). Casapase is expressed within cells as inactive precursor enzyme which once it is activated by apoptosis initiation, it will resulting in biochemical and morphological changes of apoptosis (Concannon & Samali, 2003). As previously mentioned, our protein was a mutant of sHsp family where aspartic acid at position 109 has been deleted. As caspase play essential role in apoptosis, the deletion of this precursore enzyme resulted in the deletion of the function. According to Concannon & Samali (2003), when cells are induced by stress, Hsps will be accumulated. However, at some point it will be more tolerant to cytotoxic stress. This phenomenon termed as ‘thermotollerance’. During the thermotollerance, Hsps due to its protective effect will inhibit apoptosis.

The Gene Ontology (GO) suggests that the cellular component of 1tvg is cell, cell part, intracellular and/or intracellular part that involves in cellular process and/or cell adhesion. Many of apoptotic key molecules (such as cytochrome c and pro-caspase 3) are located within mitochondria. It is suggested that many of cellular protein that function as anti-apoptotic are also located within mitochondria, thus they could prevent the release of pro-apoptotic proteins (Concannon & Samali, 2003). However, Kang et al. (2004) suggest that in normal conditions, sHsps located in cytoplasm, near golgi complex and will move to the nucleus when cell was induced by stress.

This protein was also hypothesized to be involved in cell adhesion. However, due to the lack of the RGD motif that is present in cell adhesion proteins hence we can deduce that this protein does not involve in cell adhesion (Bianchet et al., 2002).

Back to main page