lecture 7 Flashcards
what are protein domains
- distinct, stable, structural units that often have arrogated functions and fold as independent compact units
- they can move as a single entity with respect to the entire protein
- one domain is typically made of a single stretch of primary sequence
- proteins have one or more domains
Discuss the protein domains in Src Protein Kinase
- contains 4 functional domains each with a different function
- Src protein kinase is one protein
- each domain is made from a single stretch of primary sequence
- contains elements of secondary structures
why are some proteins intrinsically disordered
Functional importance
- binding
- tethering
- scaffolding
- flexibility
What affect do non covalent bonds have on proteins
- they help proteins fold and maintain their structure
List the types of non- covalent interactions that help proteins fold and maintain shape
- Van Der Waal interactions
- electrostatic interactions
- hydrophobic interactions
- hydrogen bonds
How do covalent bonds help stabilize proteins?
- primarily achieved through disulfirame bonds which are formed between 2 cysteine residues
- they do not form in cytosol because it has a high concentration of reducing agents
Disulfide bonds
- are very strong
- can make proteins like keratin very tough
where is keratin found
- hair and nails
what are the 4 representations of protein conformations?
- Backbone: shows the backbone
- Ribbon: shows the backbone and emphasizes secondary structure
- Wire: shows backbone and emphasizes side chain
- Space filing: provides contour map of surface
What are the two major groups of protein
- fibrous protein
- globular protein
Fibrous proteins
- possesses property that give strength and/or flexibility- important for structural functions
- example: a-keratin, silk, elastin, collagen
globular proteins
- roughly spherical in shape and often contain several types of secondary structures
- example: myoglobin, lysozyme, cytochrome
a coiled coil composed of two a-keratin chains is
left handed
silk has small
small r groups
Why is fibroin rich in Ala and Gly
- permits close packing of B-sheets and interlocking arrangements of R groups
- also participates in van der waal interactions which help stabilize stacked structures
why are globular proteins structurally diverse
diverse functions:
- enzymes
- motor proteins
- regulatory proteins
What native state
- in general, all molecules of a given protein species adopt the same 3D conformations despite the countless folding possibilities
- usually (but not always) the most stable state (lowest energy) of a folded protein
why are only few of many possible polypeptide chains useful
- most proteins do not fold into stable proteins, others may be harmful to the cell by causing unwanted interactions
- even small changes can dramatically affect a proteins function (sickle cell anemia)
If the Glu from hemoglobin a was mutated to another amino acid, which amino acid would be most likely to result in a preservation of the function of the hemoglobin?
- aspartic acid because they are both negatively charged (acidic)
Protein denaturation
- destruction of the native structure by breaking weak bonds responsible for secondary and tertiary structures
what does the term abrupt mean
- transition from folded to unfolded state
what are the common causes of protein denaturation
- changes in temperature
- extreme pH
- detergents or organic solvents
- urea or guanidinium chloride
- reducing agent
what are chaperone proteins
- many proteins can fold without any additional help
- some rely on chaperone proteins which help with the folding process through various mechanism
- for example: formation of isolation chambers to prevent polypeptide chains from aggregating with either other molecules or itself in the cytoplasm
- may also bind to hydrophobic residues of nascent polypeptides preventing unwanted associations with other hydrophobic residues
what are some diseases that arise as a result of misfiled proteins
- alzheimer’s disease
- huntingtons disease
- creutzfeldt-jakob disease
- “mad cow” disease
Describe the Chris Anfinsen refolding experiment
- starts in a native state and added urea and mercapto-ethanol
- this protein is forced into an unfolded state (inactive) and disulfide cross links reduce to yield cys residues
- removal of urea and mercapto-ethanol
- disulfide cross links are correctly reformed and protein goes back to its native state
What is the Anfinsen dogma? Is this true for all proteins?
- The 3D structure of a protein is is determined only by its protein amino acid sequence
- this is generally true only for small proteins (some must fold during protein synthesis (translation) and some may need the help of chaperones)
