Knob-socket mapping of tertiary packing changes: A Case Study of Lysozyme Mutants

Poster Number

28

Lead Author Major

Chemistry and Biology

Format

Poster Presentation

Faculty Mentor Name

Jerry Tsai

Faculty Mentor Department

Chemistry

Additional Faculty Mentor Name

Hyun Joo

Abstract/Artist Statement

The knob-socket model is a novel approach to analyze and describe the tertiary packing of protein structure based on the interaction of amino acid residues. The knob-socket motif is a clique of residues that represents the basic building block of protein packing as a four body interaction between a three body “socket” surface from one secondary structure element that packs a single residue knob from another secondary structures element. As an intuitive abstraction of protein tertiary structure, the knob-socket topology map presents the three-dimensional (3D) packing structure projected into two-dimensions (2D). To understand the structural effect of mutations, the knob-socket topologies of wild type lysozyme and its mutants were mapped. From 3D structures, 2D secondary structural lattices for α-helices, β-sheets, and coils are created using the knob-socket motif. The knob-socket interactions were added on the 2D knob-socket map. The 2:1+1, 3+1, and 3:1 cliques that correspond to knob-sockets are mapped, and the 2:1 cliques representing free-sockets are implied in the 2D lattices. Using a color scheme, the protein map clearly identifies the residue contacts from different secondary structures that form a protein’s tertiary structure. After analysis of wild type lysozyme, a number of mutant structures of the lysozymes were mapped out using the same procedure. The differences incurred by mutations are analyzed by comparing the maps, and the effects of specific mutations on structures, stabilities and functions will be discussed. As this work demonstrates, the knob-socket analysis provides a new and simple way to understand protein packing structure and residue interactions as well as changes upon residue mutation.

Location

DeRosa University Center, Ballroom

Start Date

25-4-2015 10:00 AM

End Date

25-4-2015 12:00 PM

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Apr 25th, 10:00 AM Apr 25th, 12:00 PM

Knob-socket mapping of tertiary packing changes: A Case Study of Lysozyme Mutants

DeRosa University Center, Ballroom

The knob-socket model is a novel approach to analyze and describe the tertiary packing of protein structure based on the interaction of amino acid residues. The knob-socket motif is a clique of residues that represents the basic building block of protein packing as a four body interaction between a three body “socket” surface from one secondary structure element that packs a single residue knob from another secondary structures element. As an intuitive abstraction of protein tertiary structure, the knob-socket topology map presents the three-dimensional (3D) packing structure projected into two-dimensions (2D). To understand the structural effect of mutations, the knob-socket topologies of wild type lysozyme and its mutants were mapped. From 3D structures, 2D secondary structural lattices for α-helices, β-sheets, and coils are created using the knob-socket motif. The knob-socket interactions were added on the 2D knob-socket map. The 2:1+1, 3+1, and 3:1 cliques that correspond to knob-sockets are mapped, and the 2:1 cliques representing free-sockets are implied in the 2D lattices. Using a color scheme, the protein map clearly identifies the residue contacts from different secondary structures that form a protein’s tertiary structure. After analysis of wild type lysozyme, a number of mutant structures of the lysozymes were mapped out using the same procedure. The differences incurred by mutations are analyzed by comparing the maps, and the effects of specific mutations on structures, stabilities and functions will be discussed. As this work demonstrates, the knob-socket analysis provides a new and simple way to understand protein packing structure and residue interactions as well as changes upon residue mutation.