Crystallin

CrysTalline

CrysTallinBy Group 94: Jade B., Kayla B., & Travis B.

Opening CreditsCrystallins are the predominant structural proteins in our eyes.It lies right behind the iris and it is what focuses the light to the retina.They are tiny heat shock proteins that prevent misfolding of other proteins in the eye.B-crystallin expression in the retina, heart, skeletal muscles, skin, brain and other tissues.Main focus of research is directed towards the lens of the eye.Tell you how it is related to Breast Cancer.

StructureA major lens protein comprising up to 40% of total lens proteinsIt is a polydisperse molecule consisting of a 3:1 ratio of Alpha A to Alpha B subunitsIt is about 90 amino acids long consisting of: Arg, Cys, His, Iso, Leu, Lys, Met, Phe, Thr, Tyr, and Val.Too big to analyze with NMR, so little is known about the structure.

Function

The B-crystallin is a molecular chaperone and a heat shock protein.This prevents any misfolding from happening in the lens.The protein allows the lens to tolerate aging-induced deterioration of the lens.This stops cataracts from forming for a while.

Kinetics

B-crystallin also takes place in oligomerization with other crystallins in the lens.Oligomerization: A production of a longer protein chain through the interaction of two or more monomers.The gamma-crystallin acts as weak glue to bind the proteins together.This oligomerization is pH dependent; when the pH becomes more basic then the protein-protein interactions stop thus cataracts begin to form.If the pH stays higher than 7, then cataracts will still form.Protein-protein interaction is very important for B-crystallin, otherwise the aging process will begin.

Regulation

The Pax6 and c-Maf genes regulate multiple mammalian stages in lens development.Pax6 binds to DCR1 of the B-crystallin gene to promote higher levels of c-Maf from cromatin to bind.Once the c-Maf binds to B-crystallin the proteins needed to keep the lens from aging are released.These genes are released due to the pH change from the protein-protein binding.

Evolution & Orthologues

In humans B-crystallin it is thought to be the cause of recent gene duplication.Motif 3 and 1 face the outside of the protein so they are more affected by environmental factors.This protein is found in rats as well; their motif 3 is less conserved just like humans are.This is thought to have evolved into the gamma-crystallin that helps bind the proteins today.With the strong selective pressure on the outside motifs it helps with the ion pairs from the motifs to create a more transparent lens.

Story: Cataracts

Story: Breast Cancer

Closing creditsCrystallin is found throughout the body but is predominantly in the lens of the eyeIt is a large molecule that is made up of two different subunitsIt functions as a chaperone protein in order to prevent the misfolding of other proteinsCrystallin acts as a weak glue and acts in oligomerization with other crystallin proteinsDuring regulation of the crystallin, pH changes cause the release of the proteins needed to keep the lens from agingCrystallin has evolved to help prevent cataracts from forming and can be linked to breast cancer

ReferencesMain slide: http://upload.wikimedia.org/wikipedia/commons/f/fe/Duck_Delta_1_Crystallin.jpgStructure: https://www.ncbi.nlm.nih.gov/pubmed/10627817, https://www.ncbi.nlm.nih.gov/pubmed/15575808, http://www.boxingscene.com/nutrition/9205.php, http://www.miramareyelooks.com/images/clear-lens_225w.jpgFunction: https://www.ncbi.nlm.nih.gov/pubmed/17166758, https://www.amherst.edu/people/facstaff/pbohara/Research/alpha.crystallinKinetics: https://www.amherst.edu/people/facstaff/pbohara/Research/alpha.crystallin, http://www.thefreedictionary.com/oligomerizationRegulation: https://www.ncbi.nlm.nih.gov/pubmed/16675956Evo/Orhto: file:///C:/Users/burto/OneDrive/Documents/biomolecule%20challenge%20paper.pdf http://www.sciencedirect.com/science/article/pii/0079610788900107Cataracts: https://pdb101.rcsb.org/motm/127Breast Cancer: http://www.scienceworldreport.com/articles/11985/20140106/protein-linked-to-breast-cancer-that-spreads-to-the-brain.htm