Protein Structure and Function Pt. 1

Chapter 3

protein sequence specifies folding into secondary and tertiary structures that wither are

functional units or can interact with other peptides to form quaternary structure functional units

exceptional conformational flexibilities of disordered proteins

to their multiple functions

some polypeptides with dissimilar sequences fold into

similar 3D structures

homologous proteins evolved from a common ancestor, have similar sequences, structures, and functions, and

can be classified into families and superfamilies

proteins are polymers composed of

amino acids

human genome

21,00 protein-encoding genes that through alternative splicing of mRNAs and post-translational modifications generate hundreds of thousands of distinct protein activities

protein hierarchical structure

primary, secondary, tertiary, quaternary, supramolecular complexes

primary structure

linear sequence of amino acids linked by peptide bonds

secondary structure

local alpha-helices or beta-sheets

tertiary structure

peptide three-dimensional shape

quaternary structure

association into mutlipeptide complexes

supramolecular complexes

can be very large, consisting of tens to hundreds of subunits

proteins functions

depend on specific binding interactions and conformational changes in the structure of a properly folded protein

protein functions - structure

organizing the genome, organelles, cytoplasm, protein complexes, and membranes in three-dimensional space

protein functions - regulation

controlling protein activity

protein functions - signaling

monitoring the environment and transmitting information

protein functions - enzyme activity

catalyzing chemical reactions

protein functions - motor

generating force for movement

primary structure - protein structure

derived from 3D structure, which is determined by amino acid sequence and intramolecular molecular non covalent interactions

structure of polypeptide - proteins

unbranched polymers constructed out of 20 amino acids with different R group side chains

amino acid side chains determine the

distinct properties of individual proteins

peptide bond

formed by a dehydration reaction linking one amino acid C-terminus and to another animo acid N-terminus

polypeptide

linear polymer has a free amino acid (N-terminus) and a free carboxyl end (C-terminus)

change in amino acid due to a

point mutation

affect on structure depends on

nature of side chain

secondary structure refers to the

conformation of adjacent amino acids into a-helix and beta-sheets, hinges, turns, loops, or finger-like extensions

secondary structure formation -

stable spatial arrangements of polypeptide chains segments held together by hydrogen bonds between backbone amide and carbonyl

polypeptide backbone folds into a

spiral/helix and then is stabilized by hydrogen bonds between backbone oxygen and hydrogen atoms

R-groups project outward from the surface of the helix -

determine chemical nature of helix faces

prolines - can’t participate in

hydrogen bonding and usually are excluded from an alpha helix

beta sheet structure

laterally packed beta strands, each of which is a nearly fully extended polypeptide

bets sheets are stabilized by

hydrogen bonds between backbone oxygen and hydrogen atoms in amino acids on different strands

tertiary structure is the conformation of the

entire polymer

tertiary structure stabilized primarily by

hydrophobic and Van der Waals interactions between non polar side chains and hydrogen bonds involving polar side chains and backbone amino and carboxyl groups

proteins can be

fibrous or globular

hydrophobic residues

cluster together like drops of oil in the folded proteins core, driven away from the aqueous surroundings by the hydrophobic effect

charged and uncharged polar side chains

form stabilizing interactions with surrounding water and ions on the protein surface

the formation of noncovalent bonds results in

a release in energy and a more stable macromolecular structure (lower energy state)

proteins fold into a 3D shape that requires the

least amount of energy to maintain

well-ordered proteins

globular proteins, fibrous proteins, integral membrane proteins

globular proteins

generally water-soluble, compactly folded structure, often but not exclusively spheroidal in shape

fibrous proteins

large, elongated, often stiff molecules

integral membrane proteins

embedded within the phospholipid bilayer of membranes

intrinsically disordered proteins

do not have well-ordered structures, very flexible, interact with partner proteins

induced fit

the interaction between two molecules results in conformational changes that changes that allow the molecules to interact with greater affinity for one another

structural motifs

• regular combinations of secondary structure usually with a specific type of function

• can be encoded by a highly conserved sequence motif

coil-coil motif

two alpha helices wound around each other

EF hand

a type of helix-loop-helix motif in many proteins, including many calcium-bind and DNA-binding regulatory proteins

zinc-finger motif

present in many DNA-binding proteins that help regular transcription

proteins domains occur

when proteins are composed of two or more distinct regions

three main classes of proteins domains

functional, structural, topological

functional domain

region of protein that exhibits a specific activity, usually independent of other regions of the protein

structural domain

regions of >40 amino acids arranged in a single, stable, distinct structure often comprised of one or more secondary structures

topological domain

regions of proteins defined by their spatial relationship to the rest of the protein; e.g., membrane spanning proteins have extracellar, membrane embedded and cytoplasmic domains

epidermal growth factor (EGF) precursor

generated by proteolytic cleavage generates multiple EGFs

Neu (EGF)

EGF domain plus other domains

tissue plasminogen activator (TPA)

EGF domain plus other domains

quaternary structure refers to proteins

composed of subunits (it refers to the manner in which subunits interact)

protein-protein interactions

different proteins can become physically associated to form a multiprotein or supramolecular complexes

protein amino acid sequence determines its

3D structure and function

misfoled/denatured proteins can form well-organized

amyloid fibril aggregates that can cause diseases

planar peptide bonds limit

the shapes into which proteins can fold

planar peptide bonds are generally in

trans configuration

in peptide bonds, the carbonyl carbon and amide nitrogen must

lie in a fixed plane; little rotation of the peptide bond is possible

the only flexibility in a polypeptide chain is

rotation of the fixed planes of adjacent bonds

native state

usually the conformation with the lowest free energy (G)

molecular chaperones are

“helper proteins” to prevent nonselective interactions during protein folding to achieve proper 3D conformation

molecular chaperones bind to

short segment of a protein substrate and stabilize unfolded or partly folded proteins, preventing aggregation of degradation

chaperonins

folding chambers into which all or part of an unfolded protein can be bound in an appropriate environment, giving it time to fold properly