{"597628":{"#nid":"597628","#data":{"type":"news","title":"\u2018Y\u2019 a Protein Unicorn Might Matter in Glaucoma","body":[{"value":"\u003Cp\u003ESo unheard of was a discovery that researchers made in a protein associated with glaucoma that for over two years they ran it \u003Ca href=\u0022http:\/\/www.cell.com\/structure\/fulltext\/S0969-2126(17)30299-X\u0022 target=\u0022_blank\u0022\u003Ethrough a gauntlet of lab tests and published a new research paper on it.\u003C\/a\u003E The tests validated what they initially saw.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIt was a Y-shape. That made it an extreme oddity significant to science, and possibly someday to medicine, too, particularly in the treatment of certain types of blindness.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;A protein like this one has never been reported before. There are extremely few Y-shapes in \u003Ca href=\u0022http:\/\/www.yourdictionary.com\/protein\u0022 target=\u0022_blank\u0022\u003Eprotein\u003C\/a\u003Es at all,\u0026rdquo; said Raquel Lieberman, who led the study. Lieberman is a structural biologist at the Georgia Institute of Technology, and an expert on myocilin, a protein sometimes\u0026nbsp;\u003Ca href=\u0022http:\/\/www.glaucoma.org\/glaucoma\/the-genetics-of-glaucoma-what-is-new.php\u0022 target=\u0022_blank\u0022\u003Eimplicated in a form of hereditary glaucoma\u003C\/a\u003E.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Ca href=\u0022https:\/\/nei.nih.gov\/health\/glaucoma\/glaucoma_facts\u0022 target=\u0022_blank\u0022\u003EGlaucoma\u003C\/a\u003E is the second most common cause of blindness globally, and hereditary glaucoma is just one category of the disease. Genetic mutations in myocilin are a major cause of hereditary glaucoma, which can strike at a particularly young age, including in childhood.\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003E\u0026#39;Absolutely unique\u0026#39;\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EThere are other shapes in proteins that look similar to the Y, but there are key differences.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;Antibodies look a little like this, but \u003Ca href=\u0022http:\/\/www.biology.arizona.edu\/immunology\/tutorials\/antibody\/structure.html\u0022 target=\u0022_blank\u0022\u003Ein antibodies, separate proteins\u003C\/a\u003E that are the products different genes fit together to make a kind of Y-shape,\u0026rdquo; Lieberman said. \u0026ldquo;This Y is encoded by one single gene sequence. That makes this absolutely unique.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn addition to being the ostensible unicorn of protein structures, it turned out to be the central binding element of myocilin. The Y ties together major components to nail down myocilin\u0026rsquo;s overall form, overturning previous conceptions about the protein\u0026#39;s appearance.\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003EMyocilin and blindness\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EAlthough the Y hasn\u0026rsquo;t been particularly implicated in glaucoma, its existence could meaningfully alter the way researchers understand myocilin and how it works in the eye. When myocilin \u003Ca href=\u0022https:\/\/ww2.chemistry.gatech.edu\/lieberman\/research\u0022 target=\u0022_blank\u0022\u003Egoes wrong, or \u0026ldquo;misfolds,\u0026rdquo;\u003C\/a\u003E it makes \u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3323732\/\u0022 target=\u0022_blank\u0022\u003Efibrils\u003C\/a\u003E that damage tissue called the \u003Ca href=\u0022http:\/\/westmetroeye.com\/wp-content\/uploads\/2016\/05\/image002.jpg\u0022 target=\u0022_blank\u0022\u003Etrabecular meshwork\u003C\/a\u003E that normally allows the fluid inside the eye to drain and relieve interior pressure.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;If you kill the cells that make this drainage work, it\u0026rsquo;s going to clog, and pressure inside the eye will increase,\u0026rdquo; said Lieberman, who is an \u003Ca href=\u0022https:\/\/ww2.chemistry.gatech.edu\/lieberman\/principal-investigator\u0022 target=\u0022_blank\u0022\u003Eassociate professor in Georgia Tech\u0026rsquo;s School of Chemistry and Biochemistry\u003C\/a\u003E. That pressure can kill parts of the retina or optic nerve, leading to irreversible partial or total blindness.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EBut though myocilin is common in many parts of our bodies, its normal, healthy role in the eye and, for that matter, what functions the protein has in the body at all are still a mystery.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;I think if we knew what this protein was doing in the \u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4209746\/\u0022 target=\u0022_blank\u0022\u003Etrabecular meshwork\u003C\/a\u003E, we would understand much more about glaucoma in general,\u0026rdquo; Lieberman said. \u0026ldquo;This research lets us know more about what myocilin is.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ELieberman published her \u003Ca href=\u0022http:\/\/www.cell.com\/structure\/fulltext\/S0969-2126(17)30299-X\u0022 target=\u0022_blank\u0022\u003Eresults on October 19, 2017, in the journal \u003Cem\u003EStructure\u003C\/em\u003E\u003C\/a\u003E. \u0026nbsp;The research was funded by the National Eye Institute and the National Institute of General Medical Sciences, both at the National Institutes of Health, by the National Science Foundation, and by the U.S. Department of Energy Office of Science.\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003EPropellers come undone\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EThe focus of studies so far has been on a part of myocilin that is\u0026nbsp;the main culprit in a form of hereditary glaucoma, a \u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23129764\u0022 target=\u0022_blank\u0022\u003Eprotein structure called the olfactomedin domain\u003C\/a\u003E, which Lieberman has also studied extensively. It looks like a protein \u003Ca href=\u0022https:\/\/www.chemistry.gatech.edu\/sites\/www.chemistry.gatech.edu\/files\/styles\/medium\/public\/Lieberman_Jan2015.jpeg?itok=DvhQCvNc\u0022 target=\u0022_blank\u0022\u003Epropeller\u003C\/a\u003E with five blades that surround a hole in the center.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;When a myocilin propellor misfolds, it unravels and forms \u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2634529\/\u0022 target=\u0022_blank\u0022\u003Eamyloid fibrils\u003C\/a\u003E (stringy abnormal proteins) that kill cells that maintain the trabecular network,\u0026rdquo; Lieberman said. \u0026quot;Until now, our work led us to believe that the propellers floated around individually as independent units, and not bound together in groups.\u0026quot;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;All we knew before was that, in solution, those olfactomedins were just \u003Ca href=\u0022http:\/\/www.dictionary.com\/browse\/monomer\u0022 target=\u0022_blank\u0022\u003Emonomers\u003C\/a\u003E. They didn\u0026rsquo;t seem to make up anything of a higher order, except when they unraveled into amyloid fibers, stuck together and blocked fluid flow,\u0026rdquo; Lieberman said.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Ca href=\u0022http:\/\/www.rh.gatech.edu\/news\/595769\/flesh-eating-leishmania-come-closer-vaccine-against-them-does-too\u0022 target=\u0022_blank\u0022\u003EAlso READ: A fake virus unleashes immune\u0026nbsp;system on an ugly tropical disease\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003ESuper sticky Y\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EThe Y alters the picture.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIt anchors the propellers in groups of four. Two propellers (olfactomedin domains) each appear to be connected to either tip of the Y\u0026rsquo;s branches probably by amino acid strings. With the Y, the overall myocilin looks like four pinwheels on strings tied to a slingshot.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAdding to the new discoveries: The Y\u0026nbsp;itself is sticky, like glue. It\u0026rsquo;s even annoying to handle in the lab.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;It was sticking to the plastic, sticking to the glass, sticking to the membrane, to beads,\u0026rdquo; Lieberman said. \u0026ldquo;It\u0026rsquo;s super sticky. That may serve a biological function.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EPerhaps the Y fastens the propellers to surfaces. It\u0026rsquo;s not yet known. \u0026ldquo;But we think the main function is to pair and separate out these olfactomedin domains,\u0026rdquo; Lieberman said.\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003ERevisiting misfolding\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EMutations in the Y aren\u0026rsquo;t significantly associated with glaucoma. \u0026ldquo;When it mutates, it misfolds, but not in a way that causes all that cell death,\u0026rdquo; Lieberman said.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EBut in its normal role, the Y just might promote the speed of misfolding of the propeller protein (olfactomedin domain) that\u0026rsquo;s implicated in hereditary glaucoma. When misfolded proteins come into contact with good proteins, the misfolded ones tend to make the good ones misfold, too.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;If these propeller proteins are clustered together because of the Y, and one of them misfolds, it\u0026rsquo;s going to recruit the others,\u0026rdquo; Lieberman said. \u0026ldquo;Having them tied together in groups will only magnify the contagion.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003ESlinkys make a Y\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EThe Y-shape, also termed\u0026nbsp;tripartite, is made up of what are called \u0026ldquo;coiled coils.\u0026rdquo; They\u0026rsquo;re pairs of short protein coils, a bit like two pieces of Slinky or coiled telephone cords, and they can be stretched similarly to a Slinky and then contract back in a similar way.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ECoiled coils are very common in our bodies.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;Coiled coils represent three to five percent of our genome,\u0026rdquo; Lieberman said. \u0026ldquo;They\u0026rsquo;re found in muscle contraction, in molecule transport up and down neurons. Lots of extracellular proteins (proteins that function outside of cells) also have them.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe Y\u0026rsquo;s branches are each a pair of coiled coils, each called a dimer, and in the trunk, they come together to form a group of four coiled coils called a tetramer.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Ca href=\u0022http:\/\/www.rh.gatech.edu\/news\/596973\/fight-against-top-killer-clogged-arteries-garners-acclaimed-nih-award\u0022 target=\u0022_blank\u0022\u003EAlso READ: New nano-fight against #1 killer clogged arteries\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cem\u003ECoauthors of this study were Shannon Hill, Elaine Nguyen, Rebecca Donegan, Ath\u0026eacute;na Patterson-Orazem, Anthony Hazel, and James Gumbart. The research was funded by the National Institutes of Health\u0026rsquo;s National Eye Institute (grant R01EY021205) and National Institute of General Medical Sciences (grants 9P41 GM103622 and 1S10OD018090-01); by the National Science Foundation (grant MCB-1452464); by the U.S. Department of Energy Office of Basic Energy Sciences (contract W-31-109-Eng-38). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the sponsors.\u003C\/em\u003E\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EA protein shaped like a \u0026quot;Y\u0026quot; makes scientists do a double-take and may change\u0026nbsp;the way they think about a protein sometimes implicated in glaucoma. The Y is a centerpiece in myocilin, binding four other components nicknamed propellers\u0026nbsp;together like balloons on\u0026nbsp;strings. The Y may also make them stick to things instead of floating freely as was previously believed for years.\u003C\/p\u003E\r\n","format":"limited_html"}],"field_summary_sentence":[{"value":"Unheard of: A Y-shaped part found in the middle of a mysterious protein studied in glaucoma."}],"uid":"31759","created_gmt":"2017-10-19 17:44:47","changed_gmt":"2017-11-04 18:24:16","author":"Ben Brumfield","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2017-10-19T00:00:00-04:00","iso_date":"2017-10-19T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"597620":{"id":"597620","type":"image","title":"Glaucoma depiction BrightFocus Foundation","body":null,"created":"1508431978","gmt_created":"2017-10-19 16:52:58","changed":"1508443539","gmt_changed":"2017-10-19 20:05:39","alt":"","file":{"fid":"227814","name":"trabecular-meshwork-800.jpg","image_path":"\/sites\/default\/files\/images\/trabecular-meshwork-800.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/trabecular-meshwork-800.jpg","mime":"image\/jpeg","size":48306,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/trabecular-meshwork-800.jpg?itok=uUmLNUhY"}},"597610":{"id":"597610","type":"image","title":"New Y-protein in myocilin as artistic flower arrangement","body":null,"created":"1508429415","gmt_created":"2017-10-19 16:10:15","changed":"1508434224","gmt_changed":"2017-10-19 17:30:24","alt":"","file":{"fid":"227808","name":"cover-attempt-5.jpg","image_path":"\/sites\/default\/files\/images\/cover-attempt-5.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/cover-attempt-5.jpg","mime":"image\/jpeg","size":2377707,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/cover-attempt-5.jpg?itok=I3gbSWeh"}},"597625":{"id":"597625","type":"image","title":"Unique Y-shape protein dimer of dimers tetramer in myocilin","body":null,"created":"1508433509","gmt_created":"2017-10-19 17:18:29","changed":"1508434105","gmt_changed":"2017-10-19 17:28:25","alt":"","file":{"fid":"227815","name":"STRUCTURE-D-17-00148_R3.jpg","image_path":"\/sites\/default\/files\/images\/STRUCTURE-D-17-00148_R3.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/STRUCTURE-D-17-00148_R3.jpg","mime":"image\/jpeg","size":28911,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/STRUCTURE-D-17-00148_R3.jpg?itok=E3X3ODaV"}},"587661":{"id":"587661","type":"image","title":"Raquel Lieberman","body":null,"created":"1487627888","gmt_created":"2017-02-20 21:58:08","changed":"1487627888","gmt_changed":"2017-02-20 21:58:08","alt":"","file":{"fid":"223963","name":"Asso. Professor Raquel Lieberman.jpg","image_path":"\/sites\/default\/files\/images\/Asso.%20Professor%20Raquel%20Lieberman_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/Asso.%20Professor%20Raquel%20Lieberman_0.jpg","mime":"image\/jpeg","size":76097,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/Asso.%20Professor%20Raquel%20Lieberman_0.jpg?itok=Yw9goQIX"}}},"media_ids":["597620","597610","597625","587661"],"groups":[{"id":"1188","name":"Research Horizons"},{"id":"1278","name":"College of Sciences"},{"id":"1214","name":"News Room"}],"categories":[{"id":"135","name":"Research"},{"id":"138","name":"Biotechnology, Health, Bioengineering, Genetics"},{"id":"141","name":"Chemistry and Chemical Engineering"},{"id":"146","name":"Life Sciences and Biology"}],"keywords":[{"id":"17401","name":"Glaucoma"},{"id":"84701","name":"myocilin"},{"id":"175993","name":"Y-shape"},{"id":"175994","name":"dimer of dimers"},{"id":"175997","name":"tripartite"},{"id":"175995","name":"tetramer"},{"id":"10858","name":"Raquel Lieberman"},{"id":"175989","name":"rare discovery"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"},{"id":"71881","name":"Science and Technology"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Cstrong\u003EResearch News\u003Cbr \/\u003E\r\nGeorgia Institute of Technology\u003Cbr \/\u003E\r\n177 North Avenue\u003Cbr \/\u003E\r\nAtlanta, Georgia \u0026nbsp;30332-0181 \u0026nbsp;USA\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EMedia Relations Contact\u003C\/strong\u003E: Ben Brumfield (404-660-1408)\u003C\/p\u003E\r\n","format":"limited_html"}],"email":["ben.brumfield@comm.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}