Endoplasmic Reticulum Properties and Functions

**11**

**1. Introduction**

**Chapter 2**

**Abstract**

Reticulum

*and Christian A.M. Wilson*

Mechanical Properties of

Chaperone BiP, the Master

*Hilda M. Alfaro-Valdés, Francesca Burgos-Bravo,* 

*Nathalie Casanova-Morales, Diego Quiroga-Roger* 

Immunoglobulin heavy-chain-binding protein (BiP protein) is a 75-kDa Hsp70 monomeric ATPase motor that plays broad and crucial roles maintaining proteostasis inside the cell. Its malfunction has been related with the appearance of many and important health problems such as neurodegenerative diseases, cancer, and heart diseases, among others. In particular, it is involved in many endoplasmic reticulum (ER) processes and functions, such as protein synthesis, folding, and assembly, and also it works in the posttranslational mechanism of protein translocation. However, it is unknown what kind of molecular motor BiP works like, since the mechanochemical mechanism that BiP utilizes to perform its work during posttranslational translocation across the ER is not fully understood. One novel approach to study both structural and catalytic properties of BiP considers that the viscoelastic regime behavior of the enzymes (considering them as a spring) and their mechanical properties are correlated with catalysis and ligand binding. Structurally, BiP is formed by two domains, and to establish a correlation between BiP structure and catalysis and how its conformational and viscoelastic changes are coupled to ligand binding, catalysis, and allosterism (information transmitted between the domains), optical

tweezers and nano-rheology techniques have been essential in this regard.

chaperones is BiP protein (immunoglobulin heavy-chain binding protein).

posttranslational translocation, molecular motor

**Keywords:** immunoglobulin binding protein (BiP), optical tweezers, nano-rheology,

The endoplasmic reticulum (ER) is involved in protein synthesis and the folding, assembly, transport, and secretion of nascent proteins [1]. One of the most important functions of the ER involves the quality control (ERQC) of nascent proteins, which is accomplished by ER chaperones [2, 3]. Chaperones are proteins that assist other proteins in the folding process, facilitating correct folding pathways or providing microenvironments in which folding can occur [4]. One of the most important

Regulator of the Endoplasmic

#### **Chapter 2**
