Operone lac

Principles of protein structure and function Function is derived from structure Structure is derived from amino acid sequence Different activities and shapes of proteins due to different amino acid sequences

Four levels of protein structure Primary: amino acid sequence

Four levels of protein structure Primary: amino acid sequence Secondary: regular, repeated coiling and folding of polypeptide backbone

Four levels of protein structure Primary: amino acid sequence Secondary: regular, repeated coiling and folding of polypeptide backbone Tertiary: complete three-dimensional structure Quaternary: arrangement of subunits (in multisubunit protein)

Secondary structure Regular, repeated coiling and folding of polypeptide backbone Due to hydrogen bonding Two patterns –  (alpha) helix –  (beta) sheet

Tertiary Complete three-dimensional structure Due to weak interactions between side (R) groups as well as covalent disulfide bonds Weak interactions Hydrogen bonds Electrostatic interactions (ionic bonds) Hydrophobic interactions Van der Waals interactions

Tertiary structure formed through side chain interactions

Hydrophobic interactions

Tertiary Complete three-dimensional structure Composed of: –Motifs: specific combinations of secondary structural elements –Domains: structurally independent units

Motifs specific combinations of secondary structural elements

Domains Structurally independent units Two different binding domains to bind two different molecules

Tertiary Complete three-dimensional structure Native conformation: functional structure Most stable conformation

Tertiary Fibrous Proteins = extended filaments or Globular proteins = compact folded structure

Protein Folding Forming polypeptide chain requires energy and information (template)

Protein Folding Forming polypeptide chain requires energy and information (template) Forming native conformation requires NO additional energy or information (SELF ASSEMBLY)

Protein folding Amino acid sequence contains all information necessary for folding into a specific three- dimensional structure

Protein Folding

Many proteins fold by Assisted Self Assembly Correct assembly (native conformation) requires assistance by CHAPERONES

Protein unfolding = Denaturation Loss of structure and function –Heat –Extreme pH –Detergents –Urea

Protein unfolding = Denaturation Why do these conditions cause loss of structure and function? –Heat –Extreme pH –Detergents –Urea

Tertiary Complete three-dimensional structure Due to weak interactions between side (R) groups as well as covalent disulfide bonds

Lysozyme

Tertiary: complete three-dimensional structure Quaternary: arrangement of subunits (in multisubunit protein)

Folding dell’emoglobina Ribbon diagram

Hemoglobin

Quaternary structure Held together by weak interactions between side (R/functional) groups as well as covalent disulfide bonds

Structure-function relationship Function is derived from structure Structure is derived from sequence

Sickle-cell disease Normal red blood cells Sickle shaped red blood cells Due to single amino acid change in hemoglobin = protein carries oxygen in red blood cells

Sickle-cell disease

Single specific amino acid change causes change in protein structure and solubility Results in change in cell shape Causes cells to clog blood vessels

Structure-function relationship Function is derived from structure Structure is derived from sequence

Molecules with similar shapes can interact in similar ways. –For example, morphine, heroin, and other opiate drugs are similar enough in shape that they can bind to the same receptors as natural signal molecules, called endorphins. –Binding to the receptors produces euphoria and relieves pain. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 2.19

Structure-function relationship Function is derived from structure Structure is derived from sequence ›Similar sequences have similar functions

Structure-function relationship Function is derived from structure Structure is derived from sequence ›Similar sequences have similar functions ›Similar function often implies evolutionary relatedness (homology) »Sequence similarity suggests common evolutionary origin

Homologous proteins Similar sequence Similar structure Similar function Evolved from common ancestor Belong to protein family

Proteins Protein modification and degradation 1. Covalent chemical modification 2. Proteolytic processing and protein splicing 3. Proteolytic degradation

Reading and questions Chapter 3 Questions 3-1, 3-2, 3-8, 3-11a, 3-15a -15d -15e, 3-16