Principles of Protein Structure

AMINOACIDS

Estereoisomer L Side-chain (-CH 3 ) }carboxyl-COOH amino amino -NH 2

PEPTIDE BOND

Peptide bond | O | || _ --C — N-- | H _ | O | | --C == N-- | H-+ P LANE -CO-NH-

Angles  i   = [-180º, +180º ]  = [-180º, +180º ]

Native Conformation

STRUCTURE

Hydrogen Bond INTRA-CHAININTER-CHAIN CloseFar { donor acceptor

SECONDARYSTRUCTURE

Chain  CtNt Sheet 

Helix Helix  H ELIX Helix Turn-3 3 Aa 3.6 Aa Turn-4 HELIX

N-cap box HbondHidrophobic N c -N 3 N’-N 4 Big box N c -N 3 N’’-N 4 Shellman C’’-C 3 C’-C 2 C’’-C 3 LL C’-C 3 C’’-C 3

RAMACHANDRAN MAP    

PROPENSITY

Xray diffraction X ray = 3DStructure FourierSynthesis Crystal

PROTEIN CLASSIFICATION

MIOGLOBIN MIOGLOBIN Hydrofobic Core Core

ENERGY

HYDROFOBIC EFFECT: zone hydroph. C LATRATE Waterfree S S S S

FOLDS

TriosePhosphateIsomerase Carboxypeptidase Glucanase Ribonuclease Mioglobin

SUPERSECUNDARY STRUCTURE

MOTIF: Cluster of 2-4 regular secondary structures usually involved in a particular function Exemple: EF hand  hairpin Ca +2 binding loop

Exemple: hairpin  hairpin  Turn  2 Aa Gly TIPE I’ H.B. lost TIPE II

Binding of

DOMAIN

Baldomero Oliva Miguel

Sequence FunctionStructure Function - Structure - Sequence Orthology

Sequence Function Structure Convergence (Analogy) Function - Structure - Sequence

Sequence Function Structure convergence? Function - Structure - Sequence

Sequence Function Structure Remote Homology superfamily Function - Structure - Sequence

Sequence Function Structure Diversity Function - Structure - Sequence

Sequence Function Structure Paralogs Function - Structure - Sequence

Sequence Function Structure Annotation problem Function - Structure - Sequence

UCL, Janet Thornton & Christine Orengo Class (C), Architecture(A), Topology(T), Homologous superfamily (H) Protein Structure Classification CATH - Protein Structure Classification [ ] SCOP - Structural Classification of Proteins MRC Cambridge (UK), Alexey Murzin, Brenner S. E., Hubbard T., Chothia C. created by manual inspection comprehensive description of the structural and evolutionary relationships [ ]

Baldomero Oliva Miguel SCOP Family Superfamily Fold Class CATH Architecture Topology Superfamily Class

TSS toxin 8.8% Id RemoteHomology Cholera toxin 80% Id Homology Baldomero Oliva Miguel SCOP Family Superfamily Fold Class Enterotoxin Aminoacyl tRNA synthetase 4.4% Id Analogs

Class(C) derived from secondary structure content is assigned automatically Architecture(A) describes the gross orientation of secondary structures, independent of connectivity. Topology(T) clusters structures according to their topological connections and numbers of secondary structures Homologous superfamily (H)

ROSSMANFOLD

It binds mononucleotides (NAD, FAD, FMN, etc.). Rossman fold of flavodoxin

TRIOSEPHOSPHATEISOMERASE

HIGHLY STABLE FOLD TIM BARREL

All 

4 helix bundle

Globin-like fold Hydrophobic core Active site

All 

Topological diagram

 -propeller

Greek key  sandwich  -cristallin

Greek key Jelly-roll

 -sandwich : Immunoglobulin-like

Variable Domain Constant Domain

Antibody CDR



Open Sheet

Active site found in the Topological Switch



Membrane Proteins

integral periferic

Integrals: - helix-transmembrane. -  sheet transmembrane.

Helix transmembrane Helix transmembrane

Porin  sheet transmembrane  sheet transmembrane

Peripheral: