\tCapturing the right enzymes at the right moment<\/p>\n
But this is not all that NAC can do. In their new study, just published in\u00a0Science Advances, Ban and his colleagues from the Universities of Konstanz, Germany,\u00a0and Caltech reveal a previously unknown function: how NAC ensures the correct chemical modification of the histones H4 and H2A while they are still being synthesized.<\/p>\n
Histones are small, abundant proteins that must be produced rapidly when cells prepare for division. Eight histones assemble into so-called nucleosomes, around which DNA is wrapped and thereby compacted. Chemical modification of these proteins\u00a0while they are being synthesized\u00a0is crucial for proper chromosome function, and errors can contribute to diseases such as cancer.<\/p>\n
In their study, the researchers show that NAC brings two enzymes to the ribosome to first remove the first amino acid from the histone protein and then to\u00a0modify\u00a0the newly exposed end with an acetyl\u00a0chemical\u00a0group. Because histones are assembled very rapidly, these two processing steps must occur in the correct sequence\u00a0and\u00a0almost instantaneously.\u00a0<\/p>\n
\u201cFor histones, the time window for modifications is incredibly tight because their protein chains are very short,\u201d explains first author Denis Yudin, a doctoral student in Nenad Ban\u2019s lab. \u201cNAC ensures that the right enzyme is at the right place at exactly the right time.\u201d<\/p>\n
Structural insights open\u00a0possibilities for\u00a0therapies<\/p>\n
Other studies show that the enzyme that\u00a0modifies\u00a0histone proteins\u00a0with acetyl group, NatD,\u00a0is\u00a0frequently\u00a0overproduced in certain types of cancer, altering gene\u00a0regulation\u00a0and promoting tumor growth. NAC\u2019s control over the access of the enzyme NatD to the ribosome could therefore\u00a0provide\u00a0new insights into tumor biology.<\/p>\n
Detailed structural information about NAC and the enzymes it recruits,\u00a0including how NatD binds to one of NAC\u2019s flexible arms,\u00a0could\u00a0open up\u00a0new therapeutic strategies. These include drugs that block NatD\u2019s interaction surface or prevent its recruitment to translating ribosomes. Other diseases that result from faulty processing during ongoing translation could also\u00a0benefit\u00a0from these findings.<\/p>\n
A fundamentally changed understanding of protein biosynthesis<\/p>\n
\u201cThe new findings change our view of protein synthesis,\u201d explains Ban. \u201cThey show how coordinated and dynamic the processes at the ribosome are, and how a small complex at the tunnel exit sets the pace for a large fraction of protein production in our cells.\u201d\u00a0<\/p>\n
The insights also mean that future efforts to achieve a deeper\u00a0understanding of protein formation must necessarily take NAC\u2019s function into account. \u201cThey also point to a larger field of research emerging in my lab: the question of how NAC integrates co-translational targeting, enzymatic modification, protein folding, and assembly into a coordinated system.\u201d<\/p>\n
In this sense, NAC behaves less like a passive scaffold and more like a molecular gatekeeper. \u201cBy selectively opening or closing access to the ribosome\u00a0depending on the\u00a0type of protein that is being synthesized\u00a0NAC acts like a remarkably precise sorter that nonetheless fully obeys the principles of thermodynamics,\u201d says the ETH professor.<\/p>\n","protected":false},"excerpt":{"rendered":"Capturing the right enzymes at the right moment But this is not all that NAC can do. In…\n","protected":false},"author":2,"featured_media":72330,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":"","_share_on_mastodon":"0"},"categories":[6],"tags":[12476,6090,5779,1202,51],"class_list":["post-72329","post","type-post","status-publish","format-standard","has-post-thumbnail","category-zurich","tag-d-biol","tag-imaging-technology","tag-medicine","tag-news","tag-zurich"],"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ch\/116642190834953851","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/posts\/72329","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/comments?post=72329"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/posts\/72329\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/media\/72330"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/media?parent=72329"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/categories?post=72329"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/tags?post=72329"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}