Name: gtpase molecular switches and control
Uploaded: 2023-04-30T18:28:43.000Z
Duration: 2 min 14 s
Channel: JoVE

K12 Standards

Next Generation Science Standards

High School

Life Science

from-molecules-to-organisms-structures-and-processes

From Molecules to Organisms: Structures and Processes

HS-LS1-1

GTPases and their Regulation

גואנוזין טריפוספט, GTP, קרוב משפחה של ATP, הוא מולקולה קטנה החשובה לוויסות תפקוד החלבון. 
חלבוני G הם חלבונים המווסתים על ידי קשירת GTP. חלבונים אלה יש פעילות GTPase פנימית, כלומר כאשר GTP קשור, הם יכולים לזרז הידרוליזה שלה גואנוזין diphosphate, GDP. 
חלבוני G מחולקים לשתי קטגוריות, קטנות וגדולות. חלבוני G הקטנים, או המונומריים, הם תת-יחידה חלבונית יחידה המופעלת על ידי מסלולי איתות תוך-תאיים שונים.
לעומת זאת, חלבוני G הגדולים, או ההטרוטרימריים, מכילים שלוש תת-יחידות ומופעלים על ידי קולטנים מצומדים לחלבון G הקשורים לקרום.
GTPases פועלים כמתג מולקולרי, כאשר מצב ה-GDP בדרך כלל אינו פעיל בעוד שמצב ה-GTP פעיל. קשירת GTP ואחריה GTP להידרוליזה של התמ"ג היא חלק ממחזור התמ"ג/GTP.
המחזור מתחיל כאשר גורם חילופי גואנין, GEF, גורם לשינוי קונפורמטיבי בחלבון G שגורם לשחרור התמ"ג. 
GTP נקשר במהירות לאתר קשירת הנוקלאוטידים הריק כעת, שכן GTP נמצא בשפע בציטופלסמה. חלבון ה-G עובר כעת למצבו הפעיל עם GTP קשור. 
לחלבוני G יש פעילות GTPase פנימית להידרוליזה של המולקולה הקשורה; עם זאת, פירוק GTP על ידי האנזים הוא תהליך איטי ללא אותות תאיים נוספים.
לכן, כאשר מגיע הזמן לכבות את חלבון ה-G, חלבון מפעיל GTPase, או GAP, ייקשר וישפר את פעילות GTPase של החלבון. ה-GTP מתפרק לתמ"ג ולפוספט אנאורגני וחלבון ה-G חוזר למצבו הלא פעיל ומשלים את המחזור.

<ol>
	<li>מישרה, א. ק. ולמברייט, ד. ג. (2016). סקירה מוזמנת: GTPases קטנים והפערים שלהם. ביופולימרים, 105(8), 431–448.</li>
	<li>Toma-Fukai, S., & Shimizu, T. (2019). תובנות מבניות לגבי מנגנון הרגולציה של GTPases קטנים על ידי GEFs. מולקולות (באזל, שוויץ), 24(18), 3308.</li>
</ol>

gtpases והרגולציה שלהם

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חלבונים קושרי גואנין נוקלאוטידים (G-proteins), הידועים גם בשם GTPases, הם משפחת על של חלבונים המווסתים תהליכים תאיים רבים, כגון איתות תאים, הובלה שלפוחית וויסות צורת התא ותנועתיותם. מוטציה או חוסר תפקוד של חלבונים אלה עלולים להוביל למחלה. ישנם כ-40,000 חלבוני G ידועים שניתן לסווג באופן כללי לשתי קבוצות - חלבוני G קטנים המורכבים מתחום יחיד וחלבוני G מרובי תחומים גדולים.

חלבוני G גדולים, הידועים גם בשם חלבוני G הטרוטרימריים, מורכבים משלוש יחידות משנה - α, β ו- γ. ליחידת המשנה α יש תחום שמור המקיים אינטראקציה עם קולטנים מצומדים לחלבון G כדי לתווך איתות טרנסממברנלי.

חלבוני G קטנים הם תת-יחידה אחת ומאותתים בכל התא במגוון מסלולים. הם מחולקים לחמש תת-משפחות על סמך רצף ותפקוד - Ras, Rho, Rab, Ran ו-Arf. מוטציות בתת-משפחת ראס מובילות להיווצרות גידולים סרטניים בריאות, במעי הגס ובלבלב. תת-משפחת Rho מסדירה ארגון מחדש של אקטין ודינמיקה של שלד ציטובולי מיקרוטובולי. תת-משפחת ראב, משפחת חלבוני ה-G הקטנה הגדולה ביותר, מווסתת את הובלת שלפוחיות וסחר בממברנות במסלולי הפרשה ואנדוציטים. תת-משפחת ראן מווסתת הובלה נוקלוציטופלזמית של RNA וחלבונים דרך ההרכבה והתפקוד של הציר הגרעיני והציר המיטוטי. תת-משפחת ארף מעורבת בהובלת שלפוחיות וסחר בממברנות.

חלבוני G מוסדרים על ידי קישור GTP/GDP ויש להם פעילות GTPase מהותית, כלומר הם יכולים לבצע הידרוליזה של GTP ל-GDP. כאשר GTP נקשר, חלבון ה-G נמצא במצב "ON", כלומר החלבון יקדם אשדות איתות בתא. כאשר התמ"ג מוגבל, הוא נמצא במצב "כבוי", מה שגורם לאיתות להפסיק. ויסות הפעלת חלבון G מווסת עוד יותר על ידי גורמי חילופי גואנין נוקלאוטידים (GEFs), המסייעים בפירוק GDP, וחלבונים משפעלי GTPase (GAPs) הממריצים הידרוליזה של GTP. בנוסף, מעכבי ניתוק גואנין (GDI) יכולים להיקשר ל- GTPases קטנים ולווסת את מיקומם בממברנה או בציטופלזמה.

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GTPases והרגולציה שלהם

חלבונים קושרי נוקלאוטידים גואנין (חלבוני G), הידועים גם בשם GTPases, הם משפחת על של חלבונים המווסתים תהליכים תאיים רבים, כגון תאי ...

Education

JoVE Core

Cell Biology

ביולוגיה של התא

Unit 1

יחידה 1

Protein Function

תפקוד חלבונים

KEY TERMS AND CONCEPTS

מונחים ומושגים מרכזיים

gtpase molecular switches and control

GTPases are molecular switches that help control cell activity. They bind guanosine triphosphate, or GTP, and can change between active and inactive states. This switch-like behavior makes them important in many cell processes.

The protein is active when GTP is bound and inactive when guanosine diphosphate, or GDP, is bound. GTPases can also turn themselves off by breaking down GTP into GDP. This built-in control helps cells regulate when the protein is on or off.

Their activity is regulated by other proteins as well. Some proteins help GTPases exchange GDP for GTP, while others speed up GTP breakdown. These regulators make sure GTPases respond at the right time and in the right place.

GTPase Molecular Switches and Control

ligand binding sites

Ligand Binding Sites in Proteins

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protein-protein interfaces

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conserved binding sites

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cooperative allosteric transitions

Allosteric Changes in Protein Shape

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protein kinases and phosphatases

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gtpases and their regulation

GTPases are molecular switches that help control cell activity. They bind guanosine triphosphate, or GTP, and can change between active and inactive states. This switch-like behavior makes them important in many cell processes. The protein is active when GTP is bound and inactive when guanosine diphosphate, or GDP, is bound. GTPases can also turn themselves off by breaking down GTP into GDP. This built-in control helps cells regulate when the protein is on or off. Their activity is regulated...

covalently linked protein regulators

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protein complexes with interchangeable parts

protein-complexes-with-interchangeable-parts

Modular Protein Complexes in Cells

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mechanical protein function

Proteins That Generate Cell Movement

Mechanical proteins help cells and tissues move. They turn chemical energy into force and motion. This process is important in many biological systems. These proteins are also called motor proteins. They interact with cell structures and can produce directed movement. In muscle cells, they support contraction. In other cells, they help with transport and shape changes. Mechanical protein function is a key part of how living systems work. It links protein activity to movement at the cellular...

structural protein function

Structural Proteins in Cells and Tissues

Structural proteins help cells and tissues keep their shape and strength. They are an important part of living systems because they provide support where it is needed most. Many structural proteins form fibers or other sturdy forms that resist stretching and wear. These proteins work as building materials in the body and help keep structures stable over time. Examples of structural proteins include collagen, actin, myosin, and keratin. Each one supports a different part of the body, but all...

protein networks

Mapping Protein Interaction Networks

Protein interaction networks show how proteins work together inside a cell. These networks help scientists see which proteins connect with each other and how those links support cell activity. Researchers often use online tools to build and study these networks. The transcript points to IntAct and STRING as examples of resources that can help predict and organize protein interactions. These tools make it easier to compare protein links and look for patterns in the network. Protein networks...

key terms and concepts

Explore how GTPases act as molecular switches and how GTP and GDP binding, plus regulator proteins, control when they are active or inactive.

GTPase Molecular Switches and Control | JoVE K12

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HS-LS1-2

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HS-LS1-3

GTPase Molecular Switches and Control

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