{"id":4567,"date":"2026-10-13T16:14:30","date_gmt":"2026-10-13T16:14:30","guid":{"rendered":"https:\/\/nhdbio.com\/?p=4567"},"modified":"2026-10-13T16:14:30","modified_gmt":"2026-10-13T16:14:30","slug":"%e3%83%ac%e3%82%bf%e3%83%88%e3%83%ab%e3%83%81%e3%83%89%e3%81%ae3%e5%8f%97%e5%ae%b9%e4%bd%93%e6%a7%8b%e9%80%a0%e3%82%92%e8%a7%a3%e8%aa%ac","status":"publish","type":"post","link":"https:\/\/nhdbio.com\/ja\/retatrutide-three-receptor-structure-explained\/","title":{"rendered":"1\u3064\u306e\u30da\u30d7\u30c1\u30c9\u304c3\u3064\u306e\u53d7\u5bb9\u4f53\u306b\u7d50\u5408\u3059\u308b\u4ed5\u7d44\u307f\u3068\u306f\uff1f\u30ec\u30bf\u30c8\u30eb\u30c1\u30c9\u3092\u89e3\u8aac"},"content":{"rendered":"
\n

Retatrutide's "three receptors" means the same molecule can act on three types of receptors. It is not three peptides in one vial, and it is not three receptors each contributing a fixed one-third of the effect.<\/p>\n

\"\u3053\u306e\u30ac\u30a4\u30c9\u3067\u6271\u3046\u30c8\u30d4\u30c3\u30af\u306e\u30b3\u30df\u30c3\u30af\u30a4\u30e9\u30b9\u30c8\"
\u7de8\u96c6\u7528\u30a4\u30e9\u30b9\u30c8\u3067\u3042\u308a\u3001\u5b9f\u9a13\u5199\u771f\u3067\u306f\u3042\u308a\u307e\u305b\u3093\u3002<\/figcaption><\/figure>\n

\u307e\u305a\u53d7\u5bb9\u4f53\u3092\u7406\u89e3\u3057\u307e\u3057\u3087\u3046\u3002\u3053\u308c\u306f\u5206\u5b50\u3068\u7d30\u80de\u304c\u60c5\u5831\u3092\u3084\u308a\u53d6\u308a\u3059\u308b\u90e8\u4f4d\u3067\u3059\u3002<\/h3>\n

\u53d7\u5bb9\u4f53\u306f\u7d30\u80de\u4e0a\u306e\u8a8d\u8b58\u90e8\u4f4d\u3060\u3068\u8003\u3048\u3066\u304f\u3060\u3055\u3044\u3002\u3042\u308b\u5206\u5b50\u304c\u305d\u308c\u306b\u7d50\u5408\u3067\u304d\u308b\u304b\u3069\u3046\u304b\u3001\u305d\u3057\u3066\u7d50\u5408\u5f8c\u306b\u7d30\u80de\u304c\u3069\u3046\u5fdc\u7b54\u3059\u308b\u304b\u306f\u3001\u305d\u308c\u305e\u308c\u7570\u306a\u308b\u5b9f\u9a13\u3067\u5224\u65ad\u3059\u308b\u5fc5\u8981\u304c\u3042\u308a\u307e\u3059\u3002\u5b9f\u969b\u306e\u5206\u5b50\u7d50\u5408\u306f\u5f62\u3068\u5316\u5b66\u7684\u306a\u76f8\u4e92\u4f5c\u7528\u3092\u4f34\u3044\u3001\u9375\u3068\u9375\u7a74\u306e\u6bd4\u55a9\u3060\u3051\u3067\u306f\u5341\u5206\u306b\u8aac\u660e\u3067\u304d\u307e\u305b\u3093\u3002<\/p>\n

\u3053\u3053\u306b\u793a\u30593\u3064\u306e\u540d\u524d\u306fGLP-1R\u3001GIPR\u3001GCGR\u3067\u3001GLP-1\u3001GIP\u3001\u30b0\u30eb\u30ab\u30b4\u30f3\u306b\u95a2\u9023\u3059\u308b\u53d7\u5bb9\u4f53\u306b\u5bfe\u5fdc\u3057\u307e\u3059\u3002\u8ad6\u6587\u3067R\u3068\u3044\u3046\u6587\u5b57\u3092\u898b\u305f\u3089\u3001\u307e\u305a\u53d7\u5bb9\u4f53\u3068\u7406\u89e3\u3057\u3066\u304b\u307e\u3044\u307e\u305b\u3093\u3002<\/p>\n

How do structural studies see "three kinds of binding"?<\/h3>\n

2024\u306e\u5143\u3068\u306a\u3063\u305f\u69cb\u9020\u7814\u7a76\u3067\u306f\u3001\u30ec\u30bf\u30c8\u30eb\u30c1\u30c9\u304c3\u3064\u306e\u53d7\u5bb9\u4f53\u305d\u308c\u305e\u308c\u3068\u500b\u5225\u306b\u5f62\u6210\u3059\u308b\u8907\u5408\u4f53\u3092\u89e3\u6790\u3057\u307e\u3057\u305f\u3002\u8457\u8005\u3089\u306f\u69cb\u9020\u7684\u304a\u3088\u3073\u6a5f\u80fd\u7684\u306a\u5b9f\u9a13\u3092\u7528\u3044\u3066\u3001\u5404\u53d7\u5bb9\u4f53\u304c\u3053\u306e\u30da\u30d7\u30c1\u30c9\u3092\u3069\u306e\u3088\u3046\u306b\u8a8d\u8b58\u3059\u308b\u304b\u3092\u8abf\u3079\u3001\u53d7\u5bb9\u4f53\u9593\u3067\u5171\u6709\u3055\u308c\u308b\u76f8\u4e92\u4f5c\u7528\u3068\u7279\u7570\u7684\u306a\u9055\u3044\u306b\u3064\u3044\u3066\u8b70\u8ad6\u3057\u307e\u3057\u305f\u3002<\/p>\n

"Separately" matters: it is not one molecule straddling three receptors at once in the figure. The structural figures show observations of different complexes, and colors are only there to distinguish the parts.<\/p>\n

\u69cb\u9020\u56f3\u3092\u898b\u308b\u3068\u304d\u306f\u3001\u307e\u305a3\u3064\u306e\u4f4d\u7f6e\u3092\u63a2\u3057\u307e\u3057\u3087\u3046\u3002<\/h3>\n

First find the peptide, then find the receptor's binding region, and finally see which contacts are similar across the different complexes and which change. This helps you understand that the same peptide can keep a shared recognition mode while adapting to the local structure of different receptors.<\/p>\n

The three cards in the teaching figure only represent three independent binding scenarios. They do not reproduce the original paper's atomic coordinates, nor do they show true molecular size. For the complete structure and specific residues, go back to the original paper's figures and supplementary materials.<\/p>\n

\u69cb\u9020\u304c\u7b54\u3048\u3089\u308c\u308b\u3053\u3068\u3001\u305d\u3057\u3066\u76f4\u63a5\u306b\u306f\u7b54\u3048\u3089\u308c\u306a\u3044\u3053\u3068\u306f\u4f55\u3067\u3057\u3087\u3046\u304b\uff1f<\/h3>\n

\u69cb\u9020\u306f\u8a8d\u8b58\u3068\u7d50\u5408\u306e\u8aac\u660e\u306b\u5f79\u7acb\u3061\u307e\u3059\u3002\u6a5f\u80fd\u5b9f\u9a13\u3067\u306f\u3001\u7d50\u5408\u5f8c\u306b\u751f\u3058\u308b\u30b7\u30b0\u30ca\u30eb\u3092\u4f9d\u7136\u3068\u3057\u3066\u6e2c\u5b9a\u3059\u308b\u5fc5\u8981\u304c\u3042\u308a\u307e\u3059\u3002\u81e8\u5e8a\u8a66\u9a13\u3067\u306f\u3001\u305d\u306e\u5f8c\u3001\u96c6\u56e3\u306b\u304a\u3051\u308b\u7279\u5b9a\u306e\u8a55\u4fa1\u6307\u6a19\u3092\u89b3\u5bdf\u3059\u308b\u5fc5\u8981\u304c\u3042\u308a\u307e\u3059\u3002\u3053\u308c\u30893\u7a2e\u985e\u306e\u60c5\u5831\u306f\u95a2\u9023\u3057\u3066\u3044\u307e\u3059\u304c\u3001\u540c\u3058\u7d50\u679c\u3067\u306f\u3042\u308a\u307e\u305b\u3093\u3002<\/p>\n

So you cannot directly calculate how much weight a person will lose from the shape of a binding pocket; nor can you directly assert from "three receptors" that it must be more suitable for a given person than a "dual receptor" option.<\/p>\n

\u7814\u7a76\u6750\u6599\u3092\u9078\u3076\u3068\u304d\u3001\u3053\u306e\u8ad6\u6587\u306f\u4f55\u306e\u5f79\u306b\u7acb\u3064\u306e\u3067\u3057\u3087\u3046\u304b\uff1f<\/h3>\n

\u3053\u308c\u306f\u3001\u8aad\u8005\u306b\u6750\u6599\u306e\u5b8c\u5168\u306a\u540c\u4e00\u6027\u3068\u4fee\u98fe\u3092\u78ba\u8a8d\u3059\u308b\u3088\u3046\u4fc3\u3059\u3082\u306e\u3067\u3059\u3002\u88fd\u54c1\u540d\u3001\u914d\u5217\u30c6\u30ad\u30b9\u30c8\u3001\u4ed8\u52a0\u3055\u308c\u305f\u57fa\u3001\u304a\u3088\u3073\u63d0\u4f9b\u5f62\u614b\u3092\u4e00\u7dd2\u306b\u8a18\u9332\u3059\u308b\u5fc5\u8981\u304c\u3042\u308a\u307e\u3059\u3002\u7814\u7a76\u8ad6\u6587\u306b\u8a18\u8f09\u3055\u308c\u305f\u5206\u5b50\u306f\u3001\u3044\u304b\u306a\u308b\u30ab\u30bf\u30ed\u30b0\u30ed\u30c3\u30c8\u306e\u540c\u4e00\u6027\u3001\u7d14\u5ea6\u3001\u307e\u305f\u306f\u6a5f\u80fd\u3092\u81ea\u52d5\u7684\u306b\u8a3c\u660e\u3059\u308b\u3082\u306e\u3067\u306f\u3042\u308a\u307e\u305b\u3093\u3002<\/p>\n

\u69cb\u9020\u7814\u7a76\u3092\u8aad\u3080\u305f\u3081\u306e3\u3064\u306e\u30b9\u30c6\u30c3\u30d7<\/figcaption>
\n
\u69cb\u9020\u7684\u89b3\u5bdf<\/b>\u6838\u5fc3\u7684\u306a\u554f\u3044\uff1a\u30da\u30d7\u30c1\u30c9\u304c\u7570\u306a\u308b\u53d7\u5bb9\u4f53\u306b\u3069\u306e\u3088\u3046\u306b\u7d50\u5408\u3059\u308b\u304b<\/span><\/div>\n
\u6a5f\u80fd\u5b9f\u9a13<\/b>\u6838\u5fc3\u7684\u306a\u554f\u3044\uff1a\u7d50\u5408\u5f8c\u306b\u3069\u306e\u30b7\u30b0\u30ca\u30eb\u304c\u5909\u5316\u3059\u308b\u304b<\/span><\/div>\n
\u30d2\u30c8\u7814\u7a76<\/b>\u6838\u5fc3\u7684\u306a\u554f\u3044\uff1a\u7279\u5b9a\u306e\u96c6\u56e3\u306b\u304a\u3044\u3066\u7279\u5b9a\u306e\u6e2c\u5b9a\u5024\u304c\u3069\u306e\u3088\u3046\u306b\u5909\u5316\u3059\u308b\u304b<\/span><\/div>\n<\/div>
\u6559\u80b2\u7528\u307e\u3068\u3081\u3002\u8aac\u660e\u3068\u539f\u5178\u3092\u78ba\u8a8d\u3057\u3066\u304f\u3060\u3055\u3044\u3002\u3053\u308c\u306f\u7e2e\u5c3a\u901a\u308a\u306e\u5206\u5b50\u30e2\u30c7\u30eb\u3067\u3082\u88fd\u54c1\u8a66\u9a13\u7d50\u679c\u3067\u3082\u3042\u308a\u307e\u305b\u3093\u3002<\/figcaption><\/figure>\n
\n\n\n\n\n\n\n\n
\u69cb\u9020\u7814\u7a76\u3092\u8aad\u3080\u305f\u3081\u306e3\u3064\u306e\u30b9\u30c6\u30c3\u30d7<\/caption>\n
\u30ec\u30d9\u30eb<\/th>\n\u6838\u5fc3\u7684\u306a\u554f\u3044<\/th>\n<\/tr>\n<\/thead>\n
\u69cb\u9020\u7684\u89b3\u5bdf<\/td>\n\u30da\u30d7\u30c1\u30c9\u304c\u7570\u306a\u308b\u53d7\u5bb9\u4f53\u306b\u3069\u306e\u3088\u3046\u306b\u7d50\u5408\u3059\u308b\u304b<\/td>\n<\/tr>\n
\u6a5f\u80fd\u5b9f\u9a13<\/td>\n\u7d50\u5408\u5f8c\u306b\u3069\u306e\u30b7\u30b0\u30ca\u30eb\u304c\u5909\u5316\u3059\u308b\u304b<\/td>\n<\/tr>\n
\u30d2\u30c8\u7814\u7a76<\/td>\n\u7279\u5b9a\u306e\u96c6\u56e3\u306b\u304a\u3044\u3066\u7279\u5b9a\u306e\u6307\u6a19\u304c\u3069\u306e\u3088\u3046\u306b\u5909\u5316\u3059\u308b\u304b<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n
\nTry judging for yourself: can "three receptors" be understood as a mixture of three peptides?<\/summary>\n

\u3044\u3044\u3048\u3002\u305d\u308c\u306f\u540c\u3058\u5206\u5b50\u304c3\u7a2e\u985e\u306e\u53d7\u5bb9\u4f53\u306b\u4f5c\u7528\u3059\u308b\u3053\u3068\u3092\u6307\u3057\u307e\u3059\u3002\u3042\u308b\u7269\u8cea\u304c\u6df7\u5408\u7269\u304b\u3069\u3046\u304b\u306f\u3001\u305d\u306e\u5b8c\u5168\u306a\u7d44\u6210\u3092\u5225\u9014\u78ba\u8a8d\u3057\u3066\u8abf\u3079\u308b\u5fc5\u8981\u304c\u3042\u308a\u307e\u3059\u3002<\/p>\n<\/details>\n

\n

\u5b9f\u969b\u306e\u69cb\u9020\u30c7\u30fc\u30bf\u306f\u3069\u3053\u3067\u78ba\u8a8d\u3067\u304d\u307e\u3059\u304b\uff1f<\/h3>\n

The deposited complexes are GLP-1R, PDB 8YW3 at 2.68 \u00c5; GIPR, 8YW4 at 3.26 \u00c5; and GCGR, 8YW5 at 2.84 \u00c5. One \u00e5ngstr\u00f6m is 0.1 nm. These describe overall cryo-EM resolution, not efficacy or binding percentages.<\/p>\n

\u69cb\u9020\u306e\u89b3\u5bdf\u3068\u6a5f\u80fd\u306e\u6e2c\u5b9a\u3092\u533a\u5225\u3059\u308b<\/h3>\n

\u56f31b\u306f3\u3064\u306e\u30af\u30e9\u30a4\u30aa\u96fb\u5b50\u9855\u5fae\u93e1\u306e\u7d50\u679c\u3092\u793a\u3057\u3066\u304a\u308a\u3001\u56f31e\u306f\u53d7\u5bb9\u4f53\u5909\u7570\u5f8c\u306ecAMP\u52b9\u529b\u3092\u8abf\u3079\u3066\u3044\u307e\u3059\u3002\u305d\u306e\u8ad6\u7406\u306f\u3001\u63a5\u89e6\u90e8\u4f4d\u3092\u7279\u5b9a\u3057\u3001\u90e8\u4f4d\u3092\u5909\u5316\u3055\u305b\u3001\u7d30\u80de\u5fdc\u7b54\u3092\u8a66\u9a13\u3059\u308b\u3053\u3068\u3067\u3059\u3002\u69cb\u9020\u7684\u8a3c\u62e0\u3068\u6a5f\u80fd\u7684\u8a3c\u62e0\u306f\u4e92\u3044\u3092\u88dc\u5b8c\u3057\u5408\u3044\u307e\u3059\u3002\u898b\u305f\u76ee\u306b\u8aac\u5f97\u529b\u306e\u3042\u308b\u30e2\u30c7\u30eb\u3060\u3051\u3067\u306f\u5341\u5206\u3067\u306f\u3042\u308a\u307e\u305b\u3093\u3002<\/p>\n

\u89e3\u6c7a\u3055\u308c\u306a\u304b\u3063\u305f\u9818\u57df\u3092\u78ba\u8a8d\u3059\u308b<\/h3>\n

\u69cb\u9020\u30e2\u30c7\u30eb\u306f\u5b9f\u9a13\u30c7\u30fc\u30bf\u3092\u89e3\u91c8\u3059\u308b\u3082\u306e\u3067\u3042\u308a\u3001\u751f\u304d\u305f\u7d30\u80de\u306e\u5b8c\u5168\u306a\u5199\u771f\u3067\u306f\u3042\u308a\u307e\u305b\u3093\u3002PDB\u3067\u306f\u3001\u65b9\u6cd5\u3001\u691c\u8a3c\u30ec\u30dd\u30fc\u30c8\u3001\u30e2\u30c7\u30eb\u5316\u3055\u308c\u3066\u3044\u306a\u3044\u9818\u57df\u3092\u78ba\u8a8d\u3057\u3066\u304f\u3060\u3055\u3044\u3002\u500b\u3005\u306e\u539f\u5b50\u63a5\u89e6\u3092\u8abf\u3079\u308b\u524d\u306b\u3001\u30da\u30d7\u30c1\u30c9\u3001\u53d7\u5bb9\u4f53\u3001G\u30bf\u30f3\u30d1\u30af\u8cea\u3092\u7279\u5b9a\u3059\u308b\u3053\u3068\u304b\u3089\u59cb\u3081\u307e\u3057\u3087\u3046\u3002<\/p>\n

PDB 8YW3: Retatrutide\u2013GLP-1R\u2013Gs structure<\/a> \u00b7 2024<\/p>\n

PDB 8YW4: Retatrutide\u2013GIPR\u2013Gs structure<\/a> \u00b7 2024<\/p>\n

PDB 8YW5: Retatrutide\u2013GCGR\u2013Gs structure<\/a> \u00b7 2024<\/p>\n<\/section>\n

\u539f\u5178\u3068\u53c2\u8003\u6587\u732e<\/h3>\n