FKBP


پپتیدیل-پرولیل شبه اف‌کی‌بی‌پی سیس-ترانس ایزومراز
پروتئین انسانی اف‌کی‌بی‌پی ۱۲ در اتصال به تاکرولیموس (FK506). سطح پروتئین با روش آب‌گریزی رنگ‌آمیزی شده‌است. شکاف عمیقی که لیگاند به آن می‌چسبد، آبگریز است.
شناسه‌ها
نمادFKBP_C
پی‌فمPF00254
اینترپروIPR001179
PROSITEPDOC00426
SCOPe1fkb / SUPFAM
Membranome336
تصویری از همان پروتئین در همان موقعیت فضایی

پروتئین متصل‌شونده به FK506 (انگلیسی: FK506 binding protein) که با نام اختصاری «FKBP» شناخته می‌شود خانواده‌ای از پروتئین‌ها هستند که فعالیت پرولیل ایزومرازی دارد و به لحاظ کارکرد مشابه سیکلوفیلین‌ها هستند ولی ساختار اولیه پروتئینی متفاوتی دارند.[۱] این مولکول پروتئینیی در یوکاریوت‌ها - از مخمر تا انسان - شناسایی شده و به‌عنوان شپرون تاشدگی در پروتئین‌هایی که ریشه‌های پرولینی دارند، عمل می‌کنند.[۲]

در میان این خانوادهٔ پروتئینی، FKBP12 در انسان برای اتصالش به داروی سرکوب‌کننده ایمنی تاکرولیموس قابل توجه است که در بیماران پیوند عضو و آنهایی که مبتلا به اختلالات خودایمنی هستند، استفاده می‌شود.[۳] تاکرولیموس در مقایسه با داروی سیکلوسپورین که به سیکلوفیلین متصل می‌شود، اثر بهتری در جلوگیری از رد پیوند دارد.[۴][۵] کمپلکس ترکیبی «FKBP-تاکرولیموس» و «سیکلوسپورین-سیکلوفیلین» یک آنزیم فسفاتاز به نام کلسینورین را مهار کرده و از ترارسانی پیام در مسیرهای پیام‌رسانی لنفوسیت‌های تی جلوگیری می‌کند.[۶] این اثر درمانی ارتباطی با فعالیت پرولیل ایزومرازی آن ندارد. عضو منحصر به فردی از خانوادهٔ FKBP به نام «FKBP25» یک FKBP هسته‌ای است که به‌طور غیر اختصاصی با دی‌ان‌ای متصل می‌شود و در ترمیم آن نقش دارد.[۷]

منابع

  1. ↑ Siekierka JJ, Hung SH, Poe M, Lin CS, Sigal NH (October 1989). "A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin". Nature. 341 (6244): 755–7. Bibcode:1989Natur.341..755S. doi:10.1038/341755a0. PMID 2477714. S2CID 4363530.
  2. ↑ Balbach J, Schmid FX (2000). "Proline isomerization and its catalysis in protein folding". In Pain RH (ed.). Mechanisms of protein folding (2nd ed.). Oxford: Oxford University Press. pp. 212–237. ISBN 0-19-963789-X.
  3. ↑ Wang T, Donahoe PK, Zervos AS (July 1994). "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science. 265 (5172): 674–6. Bibcode:1994Sci...265..674W. doi:10.1126/science.7518616. PMID 7518616.
  4. ↑ Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, van Hooff J, Christiaans M, Morales JM, Andres A, Johnson RW, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JL, Talbot D, Pohanka E (August 1997). "Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group". Transplantation. 64 (3): 436–43. doi:10.1097/00007890-199708150-00012. PMID 9275110.
  5. ↑ Prakash, Ajit; Rajan, Sreekanth; Yoon, Ho Sup (April 2016). "Crystal structure of the FK506 binding domain of human FKBP25 in complex with FK506". Protein Science. 25 (4): 905–910. doi:10.1002/pro.2875. ISSN 1469-896X. PMC 4941220. PMID 26749369.
  6. ↑ Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL (August 1991). "Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes". Cell. 66 (4): 807–15. doi:10.1016/0092-8674(91)90124-H. PMID 1715244. S2CID 22094672.
  7. ↑ Prakash, Ajit; Shin, Joon; Rajan, Sreekanth; Yoon, Ho Sup (2016-04-07). "Structural basis of nucleic acid recognition by FK506-binding protein 25 (FKBP25), a nuclear immunophilin". Nucleic Acids Research. 44 (6): 2909–2925. doi:10.1093/nar/gkw001. ISSN 1362-4962. PMC 4824100. PMID 26762975.

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